Details for: ANG

Gene ID: 283

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: ANG

Ensembl ID: ENSG00000214274

Description: angiogenin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 26.52
    rCSI 62.23%
    PRS 75.13
  • periportal region hepatocyte CL0019026
    CSI 15.98
    rCSI 62.13%
    PRS 75.06
  • Kupffer cell CL0000091
    CSI 15.26
    rCSI 34.91%
    PRS 74.6
  • hepatocyte CL0000182
    CSI 13.23
    rCSI 23.69%
    PRS 73.16
  • intestine goblet cell CL0019031
    CSI 11.91
    rCSI 10.57%
    PRS 71.7
  • mucus secreting cell CL0000319
    CSI 11.04
    rCSI 17.54%
    PRS 83.27
  • centrilobular region hepatocyte CL0019029
    CSI 10.58
    rCSI 27.61%
    PRS 73.88
  • epithelial cell of lung CL0000082
    CSI 7.52
    rCSI 6.24%
    PRS 74.23
  • colon goblet cell CL0009039
    CSI 7.27
    rCSI 17.28%
    PRS 80.73
  • goblet cell CL0000160
    CSI 6.45
    rCSI 6.09%
    PRS 73.05
  • paneth cell CL0000510
    CSI 6.24
    rCSI 9.21%
    PRS 85.97
  • foveolar cell of stomach CL0002179
    CSI 6.23
    rCSI 13.26%
    PRS 81.53
  • secretory cell CL0000151
    CSI 5.4
    rCSI 5.64%
    PRS 73.56
  • mucous neck cell CL0000651
    CSI 5.13
    rCSI 7.4%
    PRS 82.19
  • bronchus fibroblast of lung CL2000093
    CSI 5.11
    rCSI 4.15%
    PRS 73.69
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.16
    rCSI 5.03%
    PRS 82.28
  • fibroblast of lung CL0002553
    CSI 3.95
    rCSI 3.68%
    PRS 74.62
  • ciliated cell CL0000064
    CSI 3.88
    rCSI 6.28%
    PRS 69.39
  • stem cell CL0000034
    CSI 3.33
    rCSI 3.21%
    PRS 66.12
  • transit amplifying cell of colon CL0009011
    CSI 3.26
    rCSI 3.83%
    PRS 75.87
  • enteroendocrine cell CL0000164
    CSI 3.24
    rCSI 4.43%
    PRS 74.4
  • skin fibroblast CL0002620
    CSI 3.22
    rCSI 2.78%
    PRS 76.33
  • keratinocyte CL0000312
    CSI 3.05
    rCSI 2.56%
    PRS 76.97
  • pancreatic acinar cell CL0002064
    CSI 2.94
    rCSI 3.9%
    PRS 79.94
  • lung ciliated cell CL1000271
    CSI 2.77
    rCSI 3.2%
    PRS 65.36
  • enterocyte CL0000584
    CSI 2.77
    rCSI 4.47%
    PRS 74.3
  • ciliated epithelial cell CL0000067
    CSI 2.72
    rCSI 2.39%
    PRS 62.28
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.57
    rCSI 2.81%
    PRS 76.56
  • colon epithelial cell CL0011108
    CSI 2.45
    rCSI 2.57%
    PRS 70.93
  • intestinal epithelial cell CL0002563
    CSI 2.39
    rCSI 2.5%
    PRS 71.61
  • myoepithelial cell CL0000185
    CSI 2.32
    rCSI 5.87%
    PRS 79.83
  • basal cell CL0000646
    CSI 2.27
    rCSI 3.03%
    PRS 73.1
  • P/D1 enteroendocrine cell CL0002268
    CSI 2.09
    rCSI 11.38%
    PRS 84.09
  • multi-ciliated epithelial cell CL0005012
    CSI 2
    rCSI 2%
    PRS 67.48
  • M cell of gut CL0000682
    CSI 1.94
    rCSI 2.06%
    PRS 80.59
  • tracheal goblet cell CL1000329
    CSI 1.93
    rCSI 4.2%
    PRS 82.72
  • colonocyte CL1000347
    CSI 1.83
    rCSI 2.62%
    PRS 75.65
  • pancreatic ductal cell CL0002079
    CSI 1.81
    rCSI 3.52%
    PRS 77.01
  • small intestine goblet cell CL1000495
    CSI 1.81
    rCSI 3.96%
    PRS 80.21
  • transit amplifying cell CL0009010
    CSI 1.78
    rCSI 2.72%
    PRS 84.1
  • alveolar adventitial fibroblast CL4028006
    CSI 1.67
    rCSI 2.63%
    PRS 75.71
  • type L enteroendocrine cell CL0002279
    CSI 1.61
    rCSI 3.02%
    PRS 83.76
  • mesenchymal cell CL0008019
    CSI 1.52
    rCSI 3.87%
    PRS 67.38
  • tracheobronchial serous cell CL0019001
    CSI 1.48
    rCSI 6.4%
    PRS 82.93
  • stromal cell of ovary CL0002132
    CSI 1.36
    rCSI 3.74%
    PRS 82.53
  • pancreatic epsilon cell CL0005019
    CSI 1.36
    rCSI 6.33%
    PRS 85.29
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.13
    rCSI 2.58%
    PRS 68.46
  • peptic cell CL0000155
    CSI 1.09
    rCSI 10.71%
    PRS 86.56
  • bronchial goblet cell CL1000312
    CSI 1.04
    rCSI 4.14%
    PRS 84.31
  • type EC enteroendocrine cell CL0000577
    CSI 0.91
    rCSI 3.22%
    PRS 79.68
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.81
    rCSI 2.35%
    PRS 74.21
  • enteroendocrine cell of colon CL0009042
    CSI 0.78
    rCSI 3.66%
    PRS 85.29
  • respiratory goblet cell CL0002370
    CSI 0.49
    rCSI 5.33%
    PRS 84.25
  • acinar cell of salivary gland CL0002623
    CSI 0.1
    rCSI 2.35%
    PRS 88.1

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.

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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 [ANG](/details-gene/283) encodes angiogenin, a potent stimulator of angiogenesis and a member of the ribonuclease A superfamily. Originally identified as a human tumor-derived angiogenesis factor [Link](https://doi.org/10.1021/bi00341a031), it functions as a tRNA-specific ribonuclease, cleaving tRNA to produce tRNA-derived stress-induced RNAs (tiRNAs) that can inhibit translation or possess other regulatory functions [Link](https://doi.org/10.1016/j.molcel.2011.06.022). Its expression profile is highest in secretory and metabolically active cells, particularly various subtypes of [hepatocytes](/details-cell/CL0000182) and mucosal [goblet cells](/details-cell/CL0000160), suggesting a critical role in both systemic vascular homeostasis and local mucosal defense. Its activity is implicated in numerous physiological and pathological processes, including tissue development, wound healing, innate immunity, and tumor progression ([OMIM: [105850](https://omim.org/entry/105850)]). ## Cellular Roles and Expression Landscape The expression landscape of [ANG](/details-gene/283) highlights its primary role in secretory and barrier tissues. **Overall**, the gene shows the most significant expression in the liver, with [midzonal region hepatocytes](/details-cell/CL0019028), [periportal region hepatocytes](/details-cell/CL0019026), and [centrilobular region hepatocytes](/details-cell/CL0019029) being among the top cell types. This is complemented by high significance in [Kupffer cells](/details-cell/CL0000091), the resident macrophages of the liver, suggesting a role in liver homeostasis and immune surveillance. A second major functional niche for [ANG](/details-gene/283) is in mucosal surfaces, evidenced by its high significance in [intestine goblet cells](/details-cell/CL0019031), [colon goblet cells](/details-cell/CL0009039), and [foveolar cells of the stomach](/details-cell/CL0002179). This pattern suggests that [ANG](/details-gene/283) is a key secreted factor contributing to the chemical barrier of the gastrointestinal tract. Its expression in [epithelial cells of the lung](/details-cell/CL0000082) and [paneth cells](/details-cell/CL0000510) further supports its involvement in maintaining epithelial integrity and host defense at mucosal sites. ## Pathways and Molecular Function [ANG](/details-gene/283) is a multifunctional protein with distinct activities dependent on its subcellular location. Its canonical molecular function is its tRNA-specific ribonuclease activity ([GO:0004549](https://www.ebi.ac.uk/QuickGO/term/GO:0004549)), which is critical for its biological effects [Link](https://doi.org/10.1016/s0021-9258(19)36710-9). This enzymatic action leads to the biogenesis of tRNA-derived small RNAs (tsRNAs) ([R-HSA-9708296](https://reactome.org/content/detail/R-HSA-9708296)), which can regulate translation in response to stress ([GO:0032055](https://www.ebi.ac.uk/QuickGO/term/GO:0032055)). This ribonuclease activity is essential for its best-characterized biological process, [angiogenesis](/details-cell/GO:0001525) ([GO:0001525](https://www.ebi.ac.uk/QuickGO/term/GO:0001525)). [ANG](/details-gene/283) translocates to the nucleus of endothelial cells, a step required for its angiogenic activity, where it promotes rRNA transcription ([GO:0009303](https://www.ebi.ac.uk/QuickGO/term/GO:0009303)) and cell proliferation [Link](https://doi.org/10.1073/pnas.91.5.1677); [Link](https://doi.org/10.1016/s0006-291x(02)00479-5). This aligns with its involvement in processes like [positive regulation of endothelial cell proliferation](/details-cell/GO:0001938) ([GO:0001938](https://www.ebi.ac.uk/QuickGO/term/GO:0001938)) and its response to [hypoxia](/details-cell/GO:0001666) ([GO:0001666](https://www.ebi.ac.uk/QuickGO/term/GO:0001666)). Furthermore, functional annotations indicate a significant role in host defense. [ANG](/details-gene/283) is implicated in the [innate immune response](/details-cell/GO:0045087) ([GO:0045087](https://www.ebi.ac.uk/QuickGO/term/GO:0045087)) and exhibits direct [antimicrobial](/details-cell/GO:0061844) ([GO:0061844](https://www.ebi.ac.uk/QuickGO/term/GO:0061844)), antibacterial ([GO:0019731](https://www.ebi.ac.uk/QuickGO/term/GO:0019731)), and antifungal ([GO:0019732](https://www.ebi.ac.uk/QuickGO/term/GO:0019732)) activity. This is consistent with its high expression in mucosal barrier cells, where it is likely secreted to defend against pathogens. ## Research Directions The dual role of [ANG](/details-gene/283) in promoting tissue growth and providing host defense presents several avenues for future research, particularly in the contexts of cancer and infectious disease. Based on its expression profile and known functions, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high expression in various [goblet cells](/details-cell/CL0000160) and its antimicrobial annotations, [ANG](/details-gene/283) secreted into the gut lumen acts as a key component of the mucosal innate immune barrier. Its local tRNAse activity may generate specific tRNA-derived fragments (tRFs) that directly inhibit microbial growth or modulate the gut microbiome. 2. **Hypothesis 2:** Liver-derived [ANG](/details-gene/283), evidenced by its high expression in all [hepatocyte](/details-cell/CL0000182) subtypes, may function as a systemic 'hepatokine' that modulates vascular health and tissue repair throughout the body. Circulating levels of [ANG](/details-gene/283) could be a biomarker for liver health and its regenerative capacity following injury. A key experiment to test the first hypothesis would involve the use of intestinal organoids that differentiate to include functional [goblet cells](/details-cell/CL0000160). * **Experimental Approach:** Generate [ANG](/details-gene/283) knockout (KO) and wild-type (WT) intestinal organoids using CRISPR-Cas9. The luminal contents (secreted mucus) from both KO and WT organoids would be collected and analyzed by small RNA sequencing to identify [ANG](/details-gene/283)-dependent tRFs. Concurrently, KO and WT organoids would be challenged with pathogenic bacteria (e.g., *Salmonella typhimurium*). The outcome would be assessed by measuring bacterial invasion, organoid viability, and the expression of inflammatory markers via qPCR or RNA-seq. **Therapeutic Potential:** [ANG](/details-gene/283) is a compelling therapeutic target, primarily through **inhibition**. Its role in promoting angiogenesis is critical for the growth and metastasis of solid tumors, where it is often overexpressed [Link](https://doi.org/10.1093/oxfordjournals.molbev.a004099). Therefore, developing inhibitors of its ribonuclease activity or monoclonal antibodies that block its interaction with endothelial cell receptors represents a promising anti-cancer strategy. Such therapies could potentially limit tumor vascularization and starve tumors of essential nutrients, acting as an adjunct to conventional chemotherapy or immunotherapy.

Genular Protein ID: 4178871568

Symbol: ANGI_HUMAN

Name: Angiogenin

UniProtKB Accession Codes:

P03950 Q05CV1 Q53X86 Q6P5T2 Q8WXE7

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 1 EMBL 14 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 47 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 51 PDBsum 51 PIR 1 PRINTS 1 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 Reactome 2 RefSeq 2 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2866795

Title: Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor.

PubMed ID: 2866795

DOI: 10.1021/bi00341a032

PubMed ID: 11919285

Title: Diversifying selection of the tumor-growth promoter angiogenin in primate evolution.

PubMed ID: 11919285

DOI: 10.1093/oxfordjournals.molbev.a004099

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: 2866794

Title: Amino acid sequence of human tumor derived angiogenin.

PubMed ID: 2866794

DOI: 10.1021/bi00341a031

PubMed ID: 2440105

Title: Tissue distribution and developmental expression of the messenger RNA encoding angiogenin.

PubMed ID: 2440105

DOI: 10.1126/science.2440105

PubMed ID: 1400510

Title: Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily.

PubMed ID: 1400510

DOI: 10.1016/s0021-9258(19)36710-9

PubMed ID: 7945327

Title: Identification of the nucleolar targeting signal of human angiogenin.

PubMed ID: 7945327

DOI: 10.1006/bbrc.1994.2391

PubMed ID: 8127865

Title: Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity.

PubMed ID: 8127865

DOI: 10.1073/pnas.91.5.1677

PubMed ID: 9050852

Title: Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A.

PubMed ID: 9050852

DOI: 10.1073/pnas.94.5.1761

PubMed ID: 10413501

Title: Superadditive and subadditive effects of 'hot spot' mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A.

PubMed ID: 10413501

DOI: 10.1021/bi990762a

PubMed ID: 12051708

Title: The nuclear function of angiogenin in endothelial cells is related to rRNA production.

PubMed ID: 12051708

DOI: 10.1016/s0006-291x(02)00479-5

PubMed ID: 19354288

Title: Ribonuclease inhibitor regulates neovascularization by human angiogenin.

PubMed ID: 19354288

DOI: 10.1021/bi9005094

PubMed ID: 21855800

Title: Angiogenin-induced tRNA fragments inhibit translation initiation.

PubMed ID: 21855800

DOI: 10.1016/j.molcel.2011.06.022

PubMed ID: 8159679

Title: Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease.

PubMed ID: 8159679

DOI: 10.1073/pnas.91.8.2915

PubMed ID: 9311977

Title: Molecular recognition of human angiogenin by placental ribonuclease inhibitor -- an X-ray crystallographic study at 2.0-A resolution.

PubMed ID: 9311977

DOI: 10.1093/emboj/16.17.5162

PubMed ID: 9918722

Title: Refined crystal structures of native human angiogenin and two active site variants: implications for the unique functional properties of an enzyme involved in neovascularisation during tumour growth.

PubMed ID: 9918722

DOI: 10.1006/jmbi.1998.2378

PubMed ID: 11468363

Title: Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography.

PubMed ID: 11468363

DOI: 10.1110/ps.13601

PubMed ID: 11851402

Title: Crystallographic studies on the role of the C-terminal segment of human angiogenin in defining enzymatic potency.

PubMed ID: 11851402

DOI: 10.1021/bi015768q

PubMed ID: 12842050

Title: The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody.

PubMed ID: 12842050

DOI: 10.1016/s0969-2126(03)00131-x

PubMed ID: 14756559

Title: Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41.

PubMed ID: 14756559

DOI: 10.1021/bi035654+

PubMed ID: 9461294

Title: Three-dimensional solution structure of human angiogenin determined by 1H,15N-NMR spectroscopy -- characterization of histidine protonation states and pKa values.

PubMed ID: 9461294

DOI: 10.1111/j.1432-1033.1997.00712.x

PubMed ID: 22384259

Title: Mechanisms of loss of functions of human angiogenin variants implicated in amyotrophic lateral sclerosis.

PubMed ID: 22384259

DOI: 10.1371/journal.pone.0032479

PubMed ID: 15557516

Title: A novel candidate region for ALS on chromosome 14q11.2.

PubMed ID: 15557516

DOI: 10.1212/01.wnl.0000144344.39103.f6

PubMed ID: 16501576

Title: ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis.

PubMed ID: 16501576

DOI: 10.1038/ng1742

PubMed ID: 17886298

Title: Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis.

PubMed ID: 17886298

DOI: 10.1002/ana.21221

PubMed ID: 17900154

Title: Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis.

PubMed ID: 17900154

DOI: 10.1021/bi701333h

PubMed ID: 18087731

Title: Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis.

PubMed ID: 18087731

DOI: 10.1007/s10048-007-0111-3

PubMed ID: 17703939

Title: A novel angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy.

PubMed ID: 17703939

DOI: 10.1016/j.nmd.2007.07.003

PubMed ID: 22292843

Title: SOD1, ANG, TARDBP and FUS mutations in amyotrophic lateral sclerosis: a United States clinical testing lab experience.

PubMed ID: 22292843

DOI: 10.3109/17482968.2011.643899

PubMed ID: 25372031

Title: Computational and functional characterization of Angiogenin mutations, and correlation with amyotrophic lateral sclerosis.

PubMed ID: 25372031

DOI: 10.1371/journal.pone.0111963

Sequence Information:

  • Length: 147
  • Mass: 16550
  • Checksum: 9C462DA3C8D39ACC
  • Sequence:
    • MVMGLGVLLL VFVLGLGLTP PTLAQDNSRY THFLTQHYDA KPQGRDDRYC ESIMRRRGLT 
SPCKDINTFI HGNKRSIKAI CENKNGNPHR ENLRISKSSF QVTTCKLHGG SPWPPCQYRA 
TAGFRNVVVA CENGLPVHLD QSIFRRP