Details for: NIT1

Gene ID: 4817

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: NIT1

Ensembl ID: ENSG00000158793

Description: nitrilase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.9
    rCSI 3.52%
    PRS 71.56
  • dendritic cell, human CL0001056
    CSI 3.63
    rCSI 5.58%
    PRS 83.06
  • colon epithelial cell CL0011108
    CSI 3.49
    rCSI 3.66%
    PRS 71
  • epithelial cell of lung CL0000082
    CSI 3.33
    rCSI 2.76%
    PRS 74.28
  • interstitial cell of Cajal CL0002088
    CSI 3.19
    rCSI 4.05%
    PRS 79.4
  • immature B cell CL0000816
    CSI 3.14
    rCSI 2.33%
    PRS 85.89
  • ciliated cell CL0000064
    CSI 3.1
    rCSI 5.02%
    PRS 69.47
  • mesenchymal cell CL0008019
    CSI 2.95
    rCSI 7.49%
    PRS 67.45
  • common myeloid progenitor CL0000049
    CSI 2.88
    rCSI 2.33%
    PRS 76.1
  • duct epithelial cell CL0000068
    CSI 2.79
    rCSI 4.08%
    PRS 78.76
  • choroid plexus epithelial cell CL0000706
    CSI 2.73
    rCSI 4.47%
    PRS 63.12
  • erythrocyte CL0000232
    CSI 2.73
    rCSI 6.19%
    PRS 75.4
  • pancreatic A cell CL0000171
    CSI 2.72
    rCSI 2.85%
    PRS 77.23
  • T follicular helper cell CL0002038
    CSI 2.63
    rCSI 1.97%
    PRS 87.33
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.61
    rCSI 1.83%
    PRS 77.25
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.61
    rCSI 2.02%
    PRS 77.22
  • pro-B cell CL0000826
    CSI 2.59
    rCSI 2.15%
    PRS 76.44
  • Bergmann glial cell CL0000644
    CSI 2.52
    rCSI 3.45%
    PRS 65.92
  • retinal rod cell CL0000604
    CSI 2.52
    rCSI 4.44%
    PRS 70
  • melanocyte CL0000148
    CSI 2.5
    rCSI 1.85%
    PRS 66.91
  • Kupffer cell CL0000091
    CSI 2.4
    rCSI 5.49%
    PRS 74.64
  • cerebral cortex endothelial cell CL1001602
    CSI 2.4
    rCSI 4.15%
    PRS 64.74
  • hepatic stellate cell CL0000632
    CSI 2.4
    rCSI 8.98%
    PRS 65.99
  • goblet cell CL0000160
    CSI 2.35
    rCSI 2.22%
    PRS 73.1
  • renal alpha-intercalated cell CL0005011
    CSI 2.35
    rCSI 3.14%
    PRS 81.39
  • mesodermal cell CL0000222
    CSI 2.32
    rCSI 2.78%
    PRS 72.01
  • ionocyte CL0005006
    CSI 2.28
    rCSI 2.44%
    PRS 74.5
  • myofibroblast cell CL0000186
    CSI 2.26
    rCSI 3.13%
    PRS 72.32
  • intestinal epithelial cell CL0002563
    CSI 2.21
    rCSI 2.31%
    PRS 71.66
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.15
    rCSI 4.82%
    PRS 55.9
  • club cell CL0000158
    CSI 2.15
    rCSI 3.14%
    PRS 68.65
  • intestine goblet cell CL0019031
    CSI 2.12
    rCSI 1.88%
    PRS 71.75
  • ciliated epithelial cell CL0000067
    CSI 2.1
    rCSI 1.84%
    PRS 62.34
  • neural crest cell CL0011012
    CSI 2.07
    rCSI 1.64%
    PRS 61.55
  • hematopoietic stem cell CL0000037
    CSI 2.02
    rCSI 1.35%
    PRS 76.85
  • pancreatic acinar cell CL0002064
    CSI 1.95
    rCSI 2.59%
    PRS 79.98
  • lung ciliated cell CL1000271
    CSI 1.89
    rCSI 2.19%
    PRS 65.42
  • pulmonary ionocyte CL0017000
    CSI 1.85
    rCSI 2.25%
    PRS 80.7
  • mature B cell CL0000785
    CSI 1.84
    rCSI 1.6%
    PRS 84.1
  • enterocyte CL0000584
    CSI 1.83
    rCSI 2.94%
    PRS 74.35
  • BEST4+ enteroycte CL4030026
    CSI 1.82
    rCSI 2.26%
    PRS 75.24
  • inhibitory interneuron CL0000498
    CSI 1.78
    rCSI 4.12%
    PRS 61.88
  • stem cell CL0000034
    CSI 1.78
    rCSI 1.71%
    PRS 66.17
  • colonocyte CL1000347
    CSI 1.77
    rCSI 2.53%
    PRS 75.7
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.73
    rCSI 2.16%
    PRS 53.29
  • adipocyte CL0000136
    CSI 1.67
    rCSI 2.14%
    PRS 64.47
  • transit amplifying cell of colon CL0009011
    CSI 1.65
    rCSI 1.94%
    PRS 75.93
  • multi-ciliated epithelial cell CL0005012
    CSI 1.65
    rCSI 1.64%
    PRS 67.56
  • peripheral nervous system neuron CL2000032
    CSI 1.54
    rCSI 2.1%
    PRS 65.23
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.54
    rCSI 1.19%
    PRS 76.28
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.44
    rCSI 2.87%
    PRS 87.62
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.43
    rCSI 1.65%
    PRS 66.1
  • intestinal tuft cell CL0019032
    CSI 1.4
    rCSI 2.14%
    PRS 78.09
  • glioblast CL0000030
    CSI 1.39
    rCSI 2.22%
    PRS 65.5
  • radial glial cell CL0000681
    CSI 1.39
    rCSI 1.92%
    PRS 72.47
  • centrilobular region hepatocyte CL0019029
    CSI 1.35
    rCSI 3.52%
    PRS 73.91
  • neural progenitor cell CL0011020
    CSI 1.25
    rCSI 5.51%
    PRS 62.56
  • extravillous trophoblast CL0008036
    CSI 1.21
    rCSI 1.49%
    PRS 71.38
  • hepatocyte CL0000182
    CSI 1.19
    rCSI 2.14%
    PRS 73.21
  • placental villous trophoblast CL2000060
    CSI 1.17
    rCSI 1.81%
    PRS 72.98
  • retinal cone cell CL0000573
    CSI 1.13
    rCSI 1.81%
    PRS 63.47
  • intermediate monocyte CL0002393
    CSI 1.09
    rCSI 1.64%
    PRS 79.16
  • type B pancreatic cell CL0000169
    CSI 0.82
    rCSI 1.82%
    PRS 72.79
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.78
    rCSI 2.26%
    PRS 74.29
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.59
    rCSI 2.13%
    PRS 53.42
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.57
    rCSI 1.78%
    PRS 57.1
  • podocyte CL0000653
    CSI 0.56
    rCSI 2.5%
    PRS 74.26

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 [NIT1](/details-gene/4817) (Nitrilase 1) is a protein-coding gene located on chromosome 1q23.3 that encodes an enzyme with deaminated glutathione amidase activity. This function places it within the broader biological process of amide catabolism ([GO:0043605](https://www.ebi.ac.uk/QuickGO/term/GO:0043605)). The protein is localized to multiple cellular compartments, including the [cytoplasm](/details-cell/GO:0005737), [mitochondrion](/details-cell/GO:0005739), and [nucleus](/details-cell/GO:0005634), suggesting diverse roles in cellular metabolism and signaling. **Overall**, expression data indicate that while [NIT1](/details-gene/4817) is broadly expressed, it shows particularly high significance in hematopoietic progenitors, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), and in various immune and epithelial cell types, including [dendritic cell, human](/details-cell/CL0001056) and [colon epithelial cell](/details-cell/CL0011108). This pattern suggests a fundamental role in metabolic maintenance across diverse tissues, with specialized importance in developing blood cells and cells at environmental interfaces. ## Cellular Roles and Expression Landscape The expression profile of [NIT1](/details-gene/4817) highlights its significance across several key physiological systems. **Overall**, the gene's expression signature is most prominent in hematopoietic and immune lineages. It is a top marker in progenitor populations, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 3.90) and [common myeloid progenitor](/details-cell/CL0000049) (CSI: 2.88), suggesting a role in the early stages of blood cell differentiation. This is complemented by significant expression in mature immune cells, such as [dendritic cell, human](/details-cell/CL0001056) (CSI: 3.63), [immature B cell](/details-cell/CL0000816) (CSI: 3.14), and [T follicular helper cell](/details-cell/CL0002038) (CSI: 2.63). This pattern indicates a potential function in both hematopoietic development and the execution of innate and adaptive immune responses. Beyond the immune system, [NIT1](/details-gene/4817) shows high significance in various epithelial tissues. It is highly ranked in [colon epithelial cell](/details-cell/CL0011108) (CSI: 3.49), [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.33), and [duct epithelial cell](/details-cell/CL0000068) (CSI: 2.79). Its expression in these barrier tissues, which are often subject to metabolic and oxidative stress, is consistent with its role in glutathione metabolism. Additionally, its notable expression in specialized cell types like [interstitial cell of Cajal](/details-cell/CL0002088) and [pancreatic A cell](/details-cell/CL0000171) suggests further specialized metabolic functions in gut motility and endocrine regulation, respectively. ## Pathways and Molecular Function The functional annotations for [NIT1](/details-gene/4817) are centered on its enzymatic activity. Its primary molecular function is defined as deaminated glutathione amidase activity ([GO:0110050](https://www.ebi.ac.uk/QuickGO/term/GO:0110050)), which places it in the amide catabolic process ([GO:0043605](https://www.ebi.ac.uk/QuickGO/term/GO:0043605)). Glutathione is a critical antioxidant and a key player in cellular redox homeostasis. The ability of [NIT1](/details-gene/4817) to process a derivative of this molecule suggests it plays a role in regulating the glutathione pool or related metabolic pathways. This function provides a molecular basis for its observed expression pattern. For instance, hematopoietic progenitors and activated immune cells like dendritic cells have high metabolic demands and are exposed to significant oxidative stress, making robust redox control systems essential. Similarly, epithelial cells in the gut and lung are constantly exposed to external insults, requiring strong antioxidant defenses. The widespread subcellular localization of [NIT1](/details-gene/4817) to the [cytoplasm](/details-cell/GO:0005737), [mitochondrion](/details-cell/GO:0005739), and [nucleus](/details-cell/GO:0005634) suggests it may modulate redox-sensitive processes in multiple cellular contexts, from energy production in mitochondria to gene regulation in the nucleus. Early proteomic studies have confirmed its presence in human cell lines, supporting its role as a core component of cellular metabolism ([Link](https://doi.org/10.1186/1752-0509-5-17)). ## Research Directions The widespread yet specific expression pattern of [NIT1](/details-gene/4817), coupled with its core metabolic function, opens several avenues for future research. ### Proposed Hypotheses 1. **Role in Hematopoiesis:** Given its high significance in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), [NIT1](/details-gene/4817) may be essential for managing the metabolic and oxidative stress associated with terminal differentiation into [erythrocyte](/details-cell/CL0000232)s and platelets. Its deficiency could lead to impaired erythropoiesis or thrombopoiesis, potentially resulting in anemia or other cytopenias. 2. **Modulation of Immune Cell Function:** The high expression of [NIT1](/details-gene/4817) in [dendritic cell, human](/details-cell/CL0001056) suggests it is critical for maintaining redox balance during antigen processing and presentation. Impairment of [NIT1](/details-gene/4817) function could compromise the ability of dendritic cells to activate T cells, thereby dampening the adaptive immune response. ### Experimental Approach To test the second hypothesis regarding its role in dendritic cells, a conditional knockout of [NIT1](/details-gene/4817) could be generated in the myeloid lineage in mice (e.g., using a Lyz2-Cre driver). Bone marrow-derived dendritic cells (BMDCs) from these knockout mice and wild-type controls could be cultured and stimulated with a model antigen and a Toll-like receptor agonist (e.g., LPS). The functional consequences of [NIT1](/details-gene/4817) deletion would be assessed by measuring: (i) antigen presentation efficiency via a T cell co-culture proliferation assay; (ii) expression of co-stimulatory molecules (CD80, CD86, MHC-II) by flow cytometry; (iii) production of key cytokines like IL-12p70 and TNF-alpha; and (iv) intracellular reactive oxygen species (ROS) levels to directly link its function to redox control. ### Therapeutic Potential As an enzyme involved in glutathione metabolism, [NIT1](/details-gene/4817) could represent a therapeutic target in diseases characterized by metabolic dysregulation and oxidative stress, such as cancer. Many cancer cells exhibit increased reliance on antioxidant pathways to survive high levels of intrinsic ROS. Therefore, **inhibition** of [NIT1](/details-gene/4817) with a small molecule could be a strategy to selectively increase oxidative stress in cancer cells, potentially sensitizing them to chemotherapy or radiotherapy. However, its broad expression pattern across healthy hematopoietic and epithelial tissues poses a significant challenge, suggesting that therapeutic strategies would require targeted delivery to minimize on-target, off-tumor toxicity.

Genular Protein ID: 463524661

Symbol: NIT1_HUMAN

Name: Deaminated glutathione amidase

UniProtKB Accession Codes:

Q86X76 B1AQP3 D3DVF4 O76091

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 1 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 9 Ensembl 4 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 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 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 RefSeq 5 Rhea 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: 9671749

Title: Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans.

PubMed ID: 9671749

DOI: 10.1073/pnas.95.15.8744

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

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: 327
  • Mass: 35896
  • Checksum: 90F7FB9D4BA627B1
  • Sequence:
    • MLGFITRPPH RFLSLLCPGL RIPQLSVLCA QPRPRAMAIS SSSCELPLVA VCQVTSTPDK 
QQNFKTCAEL VREAARLGAC LAFLPEAFDF IARDPAETLH LSEPLGGKLL EEYTQLAREC 
GLWLSLGGFH ERGQDWEQTQ KIYNCHVLLN SKGAVVATYR KTHLCDVEIP GQGPMCESNS 
TMPGPSLESP VSTPAGKIGL AVCYDMRFPE LSLALAQAGA EILTYPSAFG SITGPAHWEV 
LLRARAIETQ CYVVAAAQCG RHHEKRASYG HSMVVDPWGT VVARCSEGPG LCLARIDLNY 
LRQLRRHLPV FQHRRPDLYG NLGHPLS

Genular Protein ID: 495638524

Symbol: B7Z410_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z410

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SUPFAM 1

Sequence Information:

  • Length: 312
  • Mass: 34265
  • Checksum: A26FFF9B75D24EE0
  • Sequence:
    • MTFGLRKRLS EERGFSLMPR AMAISSSSCE LPLVAVCQVT STPDKQQNFK TCAELVREAA 
RLGACLAFLP EAFDFIARDP AETLHLSEPL GGKLLEEYTQ LARECGLWLS LGGFHERGQD 
WEQTQKIYNC HVLLNSKGAV VATYRKTHLC DVEIPGQGPM CESNSTMPGP SLESPVSTPA 
GKIGLAVCYG MRFPELSLAL AQAGAEILTY PSAFGSITGP AHWEVLLRAR AIETQCYVVA 
AAQCGRHHEK RASYGHSMVV DPWGTVVARC SEGPGLCLAR IDLNYLRQLR RHLPVFQHRR 
PDLYGNLGHP LS