Details for: PIR

Gene ID: 8544

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: PIR

Ensembl ID: ENSG00000087842

Description: pirin

Cell Significance Landscape

Associated with

Significant Cells

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

  • retinal ganglion cell CL0000740
    CSI 9.39
    rCSI 20.74%
    PRS 52.32
  • respiratory suprabasal cell CL4033048
    CSI 4.74
    rCSI 6.08%
    PRS 70.83
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.92
    rCSI 14.11%
    PRS 45.96
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.76
    rCSI 4.11%
    PRS 70.19
  • retinal bipolar neuron CL0000748
    CSI 3.67
    rCSI 6.88%
    PRS 54.36
  • corneal epithelial cell CL0000575
    CSI 3.5
    rCSI 10%
    PRS 76.99
  • secretory cell CL0000151
    CSI 3.46
    rCSI 3.61%
    PRS 66.42
  • pancreatic D cell CL0000173
    CSI 3.27
    rCSI 3.22%
    PRS 69.12
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.24
    rCSI 6.17%
    PRS 80.29
  • ciliated cell CL0000064
    CSI 3.2
    rCSI 5.19%
    PRS 62.47
  • melanocyte CL0000148
    CSI 3.19
    rCSI 2.36%
    PRS 59.08
  • Mueller cell CL0000636
    CSI 3.13
    rCSI 7.14%
    PRS 57.98
  • neural crest cell CL0011012
    CSI 3.06
    rCSI 2.42%
    PRS 53.34
  • Kupffer cell CL0000091
    CSI 2.96
    rCSI 6.77%
    PRS 66.5
  • pancreatic A cell CL0000171
    CSI 2.75
    rCSI 2.88%
    PRS 69.93
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.74
    rCSI 10.35%
    PRS 48.32
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.68
    rCSI 3.46%
    PRS 48.98
  • ciliated epithelial cell CL0000067
    CSI 2.65
    rCSI 2.33%
    PRS 54.26
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.59
    rCSI 3.22%
    PRS 45.81
  • hepatocyte CL0000182
    CSI 2.54
    rCSI 4.55%
    PRS 65.79
  • choroid plexus epithelial cell CL0000706
    CSI 2.53
    rCSI 4.14%
    PRS 55.39
  • adipocyte CL0000136
    CSI 2.49
    rCSI 3.2%
    PRS 58.4
  • lung secretory cell CL1000272
    CSI 2.49
    rCSI 6.17%
    PRS 64.94
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.49
    rCSI 14.66%
    PRS 48.85
  • placental villous trophoblast CL2000060
    CSI 2.48
    rCSI 3.83%
    PRS 64.92
  • hepatic stellate cell CL0000632
    CSI 2.37
    rCSI 8.86%
    PRS 58.21
  • multi-ciliated epithelial cell CL0005012
    CSI 2.36
    rCSI 2.36%
    PRS 59.8
  • glial cell CL0000125
    CSI 2.35
    rCSI 8.94%
    PRS 56.98
  • stem cell CL0000034
    CSI 2.32
    rCSI 2.24%
    PRS 57.51
  • respiratory basal cell CL0002633
    CSI 2.3
    rCSI 2.38%
    PRS 72.14
  • cerebral cortex endothelial cell CL1001602
    CSI 2.29
    rCSI 3.96%
    PRS 56.64
  • keratocyte CL0002363
    CSI 2.28
    rCSI 5.48%
    PRS 73.19
  • vascular leptomeningeal cell CL4023051
    CSI 2.27
    rCSI 3.98%
    PRS 58.61
  • Schwann cell CL0002573
    CSI 2.22
    rCSI 6.3%
    PRS 64.15
  • pulmonary artery endothelial cell CL1001568
    CSI 2.17
    rCSI 2.96%
    PRS 77.72
  • retinal pigment epithelial cell CL0002586
    CSI 2.14
    rCSI 4.25%
    PRS 63.39
  • radial glial cell CL0000681
    CSI 2.12
    rCSI 2.95%
    PRS 64.98
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.11
    rCSI 2.53%
    PRS 47.51
  • ON midget ganglion cell CL4033046
    CSI 2.08
    rCSI 42.28%
    PRS 56.81
  • epithelial cell CL0000066
    CSI 2.05
    rCSI 3.15%
    PRS 60.29
  • chondrocyte CL0000138
    CSI 2.04
    rCSI 3.25%
    PRS 58.99
  • club cell CL0000158
    CSI 2
    rCSI 2.93%
    PRS 61.71
  • adventitial cell CL0002503
    CSI 2
    rCSI 4.77%
    PRS 74.29
  • renal interstitial pericyte CL1001318
    CSI 1.99
    rCSI 5.49%
    PRS 61.58
  • endocardial cell CL0002350
    CSI 1.98
    rCSI 9.46%
    PRS 64.52
  • type B pancreatic cell CL0000169
    CSI 1.91
    rCSI 4.22%
    PRS 64.57
  • OFF midget ganglion cell CL4033047
    CSI 1.8
    rCSI 36.72%
    PRS 58.31
  • epithelial cell of proximal tubule CL0002306
    CSI 1.79
    rCSI 4.37%
    PRS 59.36
  • cardiac endothelial cell CL0010008
    CSI 1.77
    rCSI 7.16%
    PRS 65.39
  • cardiac muscle cell CL0000746
    CSI 1.69
    rCSI 2.43%
    PRS 55.91
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.69
    rCSI 4.04%
    PRS 53.42
  • Bergmann glial cell CL0000644
    CSI 1.65
    rCSI 2.26%
    PRS 59.17
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.63
    rCSI 2.63%
    PRS 49.68
  • lung pericyte CL0009089
    CSI 1.62
    rCSI 4.27%
    PRS 75
  • direct pathway medium spiny neuron CL4023026
    CSI 1.57
    rCSI 37.65%
    PRS 46.79
  • retina horizontal cell CL0000745
    CSI 1.54
    rCSI 2.35%
    PRS 62.8
  • respiratory hillock cell CL4030023
    CSI 1.5
    rCSI 2.68%
    PRS 79.02
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.34
    rCSI 32.39%
    PRS 47.57
  • intestinal tuft cell CL0019032
    CSI 1.3
    rCSI 1.99%
    PRS 70.52
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.27
    rCSI 2.13%
    PRS 47.74
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.25
    rCSI 2.21%
    PRS 46.79
  • lung ciliated cell CL1000271
    CSI 1.24
    rCSI 1.43%
    PRS 56.89
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.18
    rCSI 3.69%
    PRS 51.86
  • forebrain radial glial cell CL0013000
    CSI 1.16
    rCSI 3.72%
    PRS 70.92
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.12
    rCSI 2.71%
    PRS 46.14
  • neural progenitor cell CL0011020
    CSI 1.11
    rCSI 4.9%
    PRS 56.2
  • endothelial cell of placenta CL0009092
    CSI 1.09
    rCSI 5.39%
    PRS 77.09
  • regular atrial cardiac myocyte CL0002129
    CSI 1.08
    rCSI 3.48%
    PRS 64.07
  • epicardial adipocyte CL1000309
    CSI 1.06
    rCSI 3.44%
    PRS 65.87
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.87
    rCSI 2.71%
    PRS 49.4
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.61
    rCSI 1.4%
    PRS 62.13
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.56
    rCSI 3.51%
    PRS 58.05
  • ON parasol ganglion cell CL4033052
    CSI 0.54
    rCSI 7.62%
    PRS 57.21
  • erythroid progenitor cell CL0000038
    CSI 0.4
    rCSI 2.28%
    PRS 74.91
  • medium spiny neuron CL1001474
    CSI 0.36
    rCSI 3.08%
    PRS 53.5
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.25
    rCSI 1.69%
    PRS 78.1

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.

Comma-separated if multiple.
Comma-separated if multiple.
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 [PIR](/details-gene/8544) (pirin) is a protein-coding gene that encodes a highly conserved, iron-binding nuclear and cytoplasmic protein. Functionally, [PIR](/details-gene/8544) is characterized as a transcription coregulator involved in processes such as [transcription by rna polymerase ii](/details-go/GO:0006366), and also possesses [quercetin 2,3-dioxygenase activity](/details-go/GO:0008127) ([Link](https://doi.org/10.1074/jbc.m501034200)). It has been identified as a cofactor for transcription factors including Bcl-3 and NF-kappaB, thereby modulating gene expression ([Link](https://doi.org/10.1038/sj.onc.1202717), [Link](https://doi.org/10.1073/pnas.1221743110)). **Overall**, the expression profile of [PIR](/details-gene/8544) shows it has a broad tissue distribution with particularly high significance in diverse specialized cell types, most notably in [retinal ganglion cells](/details-cell/CL0000740), as well as in various neuronal, epithelial, and secretory cells. ## Cellular Roles and Expression Landscape The **Overall** expression data reveals that [PIR](/details-gene/8544) has a wide-ranging but distinct cellular expression pattern. It is most significantly expressed in [retinal ganglion cell](/details-cell/CL0000740) (CSI: 9.39), suggesting a specialized and prominent role in the function of these neurons. The gene also shows significant expression in several other functional cell groups: * **Neural and Sensory Cells:** High significance is observed in [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 3.92), [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 3.67), and [Mueller cell](/details-cell/CL0000636) (CSI: 3.13), indicating a potential role in the central nervous system and retinal architecture. * **Epithelial and Secretory Cells:** [PIR](/details-gene/8544) is a significant marker in [respiratory suprabasal cell](/details-cell/CL4033048) (CSI: 4.74), [corneal epithelial cell](/details-cell/CL0000575) (CSI: 3.50), [secretory cell](/details-cell/CL0000151) (CSI: 3.46), and [ciliated cell](/details-cell/CL0000064) (CSI: 3.20). This pattern is consistent with its reported upregulation in bronchial epithelial cells in response to cigarette smoke ([Link](https://doi.org/10.1186/1465-9921-8-10)). * **Endocrine and Other Specialized Cells:** The gene is also prominent in [pancreatic D cell](/details-cell/CL0000173) (CSI: 3.27), [melanocyte](/details-cell/CL0000148) (CSI: 3.19), and the liver-resident macrophage, [Kupffer cell](/details-cell/CL0000091) (CSI: 2.96). This diverse expression landscape suggests that [PIR](/details-gene/8544) is not a lineage-defining marker but rather a functional protein involved in fundamental processes common to these varied cell types, likely related to transcriptional regulation and redox homeostasis. ## Pathways and Molecular Function [PIR](/details-gene/8544) is annotated with several key molecular and cellular functions that illuminate its biological roles. Its primary function is as a [transcription coregulator activity](/details-go/GO:0003712), consistent with its localization to the [nucleus](/details-go/GO:0005634) and specifically within the [nuclear body](/details-go/GO:0016604) ([Link](https://doi.org/10.1074/jbc.272.13.8482)). Structural and biochemical studies have confirmed it is an iron-dependent protein ([metal ion binding](/details-go/GO:0046872)) that physically interacts with transcription factors to modulate gene expression ([Link](https://doi.org/10.1074/jbc.m310022200)). Notably, [PIR](/details-gene/8544) has been shown to be a redox regulator of NF-kappaB, a critical pathway in inflammation and cell survival ([Link](https://doi.org/10.1073/pnas.1221743110)). The gene is also involved in [monocyte differentiation](/details-go/GO:0030224), and its downregulation has been implicated in impairing terminal myeloid differentiation in the context of Acute Myeloid Leukemia (AML) ([Link](https://doi.org/10.1038/leu.2009.247)). Additionally, it possesses [quercetin 2,3-dioxygenase activity](/details-go/GO:0008127), which is a catalytic function involved in flavonoid metabolism, although the physiological relevance of this activity is still being explored ([Link](https://doi.org/10.1074/jbc.m501034200)). Its association with the Reactome pathway [Digestion](/details-reactome/R-HSA-8935690) may be linked to this metabolic function. ## Research Directions Research has implicated [PIR](/details-gene/8544) in several pathological processes, including cancer progression and myeloid differentiation, opening several avenues for future investigation. Its delocalization from the nucleus to the cytoplasm is associated with melanoma progression ([Link](https://doi.org/10.1186/1471-2121-11-5)), and its downregulation is a feature of AML ([Link](https://doi.org/10.1038/leu.2009.247)). Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The exceptionally high significance of [PIR](/details-gene/8544) in [retinal ganglion cells](/details-cell/CL0000740) suggests it plays a critical neuroprotective role. It is hypothesized that [PIR](/details-gene/8544), acting as a redox-sensitive NF-kappaB coregulator, is essential for protecting these neurons from oxidative stress, and its dysregulation could be a contributing factor in the pathogenesis of neurodegenerative diseases like glaucoma. 2. **Hypothesis 2:** Given its role in [monocyte differentiation](/details-go/GO:0030224) and its suppression in AML, it is hypothesized that [PIR](/details-gene/8544) acts as a tumor suppressor in the myeloid lineage by facilitating the transcription of genes required for terminal differentiation. Its loss may cooperate with other oncogenic mutations to lock myeloid progenitors in a proliferative, undifferentiated state. A key experiment to test the second hypothesis could be designed as follows: * **Experimental Approach:** To investigate the role of [PIR](/details-gene/8544) as a tumor suppressor in AML, primary human CD34+ hematopoietic stem and progenitor cells could be transduced with a lentiviral shRNA to knock down [PIR](/details-gene/8544) expression. These cells would then be cultured in vitro under myeloid differentiation conditions. The impact of [PIR](/details-gene/8544) knockdown on differentiation would be assessed via flow cytometry for myeloid markers (e.g., CD11b, CD14), colony-forming assays to measure self-renewal capacity, and RNA-sequencing to identify the downstream transcriptional programs that are dysregulated. **Therapeutic Potential:** The involvement of [PIR](/details-gene/8544) in regulating the migration of melanoma cells, coupled with the development of a small-molecule inhibitor that blocks this function, highlights its potential as a therapeutic target ([Link](https://doi.org/10.1038/nchembio.423)). An inhibitory strategy, using small molecules to disrupt its function or its interaction with transcription factors, could be a viable approach to limit metastasis in cancers like melanoma where its activity is implicated in progression. However, the broad expression of [PIR](/details-gene/8544) across many healthy cell types suggests that systemic inhibition might carry a risk of on-target toxicity, necessitating careful therapeutic design.

Genular Protein ID: 2634569938

Symbol: PIR_HUMAN

Name: Pirin

UniProtKB Accession Codes:

O00625 Q5U0G0 Q6FHD2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 9 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 13 PDBsum 13 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9079676

Title: Identification of pirin, a novel highly conserved nuclear protein.

PubMed ID: 9079676

DOI: 10.1074/jbc.272.13.8482

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: 10362352

Title: The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators.

PubMed ID: 10362352

DOI: 10.1038/sj.onc.1202717

PubMed ID: 15951572

Title: Structural and biochemical analysis reveal pirins to possess quercetinase activity.

PubMed ID: 15951572

DOI: 10.1074/jbc.m501034200

PubMed ID: 17288615

Title: Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis.

PubMed ID: 17288615

DOI: 10.1186/1465-9921-8-10

PubMed ID: 20089166

Title: Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches.

PubMed ID: 20089166

DOI: 10.1186/1471-2121-11-5

PubMed ID: 19766747

Title: Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese.

PubMed ID: 19766747

DOI: 10.1016/j.bone.2009.09.012

PubMed ID: 20010624

Title: Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation.

PubMed ID: 20010624

DOI: 10.1038/leu.2009.247

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 14573596

Title: Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.

PubMed ID: 14573596

DOI: 10.1074/jbc.m310022200

PubMed ID: 20711196

Title: A small-molecule inhibitor shows that pirin regulates migration of melanoma cells.

PubMed ID: 20711196

DOI: 10.1038/nchembio.423

PubMed ID: 23716661

Title: Pirin is an iron-dependent redox regulator of NF-kappaB.

PubMed ID: 23716661

DOI: 10.1073/pnas.1221743110

Sequence Information:

  • Length: 290
  • Mass: 32113
  • Checksum: D06AC100F356496D
  • Sequence:
    • MGSSKKVTLS VLSREQSEGV GARVRRSIGR PELKNLDPFL LFDEFKGGRP GGFPDHPHRG 
FETVSYLLEG GSMAHEDFCG HTGKMNPGDL QWMTAGRGIL HAEMPCSEEP AHGLQLWVNL 
RSSEKMVEPQ YQELKSEEIP KPSKDGVTVA VISGEALGIK SKVYTRTPTL YLDFKLDPGA 
KHSQPIPKGW TSFIYTISGD VYIGPDDAQQ KIEPHHTAVL GEGDSVQVEN KDPKRSHFVL 
IAGEPLREPV IQHGPFVMNT NEEISQAILD FRNAKNGFER AKTWKSKIGN