Details for: ADAMTS2

Gene ID: 9509

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: ADAMTS2

Ensembl ID: ENSG00000087116

Description: ADAM metallopeptidase with thrombospondin type 1 motif 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • hepatic stellate cell CL0000632
    CSI 16.04
    rCSI 60.09%
    PRS 91.45
  • alveolar type 1 fibroblast cell CL4028004
    CSI 11.48
    rCSI 12.58%
    PRS 95.42
  • mesodermal cell CL0000222
    CSI 9.95
    rCSI 11.94%
    PRS 93.42
  • intermediate monocyte CL0002393
    CSI 8.3
    rCSI 12.52%
    PRS 96.88
  • fibroblast of lung CL0002553
    CSI 6.01
    rCSI 5.59%
    PRS 95.26
  • epicardial adipocyte CL1000309
    CSI 5.12
    rCSI 16.66%
    PRS 92.03
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.99
    rCSI 15.6%
    PRS 87.6
  • type B pancreatic cell CL0000169
    CSI 4.93
    rCSI 10.91%
    PRS 94.01
  • Kupffer cell CL0000091
    CSI 4.7
    rCSI 10.75%
    PRS 95.06
  • bronchus fibroblast of lung CL2000093
    CSI 3.84
    rCSI 3.12%
    PRS 93.85
  • lung macrophage CL1001603
    CSI 3.75
    rCSI 8.37%
    PRS 97.28
  • subcutaneous adipocyte CL0002521
    CSI 3.64
    rCSI 18.63%
    PRS 95.24
  • mesenchymal cell CL0008019
    CSI 3.43
    rCSI 8.71%
    PRS 90.67
  • adipocyte CL0000136
    CSI 3.27
    rCSI 4.2%
    PRS 87.72
  • adventitial cell CL0002503
    CSI 2.9
    rCSI 6.92%
    PRS 95.85
  • elicited macrophage CL0000861
    CSI 2.75
    rCSI 2.53%
    PRS 97.17
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.68
    rCSI 7.75%
    PRS 93.57
  • lung pericyte CL0009089
    CSI 2.52
    rCSI 6.66%
    PRS 96.72
  • vascular leptomeningeal cell CL4023051
    CSI 2.44
    rCSI 4.27%
    PRS 92.02
  • cardiac neuron CL0010022
    CSI 2.42
    rCSI 7.73%
    PRS 93.28
  • pancreatic stellate cell CL0002410
    CSI 2.33
    rCSI 13.58%
    PRS 95.18
  • renal interstitial pericyte CL1001318
    CSI 2.03
    rCSI 5.6%
    PRS 92.82
  • tendon cell CL0000388
    CSI 1.98
    rCSI 5.15%
    PRS 95.75
  • chondrocyte CL0000138
    CSI 1.92
    rCSI 3.05%
    PRS 90.87
  • contractile cell CL0000183
    CSI 1.85
    rCSI 5.47%
    PRS 94.13
  • fibroblast of cardiac tissue CL0002548
    CSI 1.83
    rCSI 8.75%
    PRS 94.95
  • parietal epithelial cell CL1000452
    CSI 1.81
    rCSI 4.85%
    PRS 90.62
  • alveolar adventitial fibroblast CL4028006
    CSI 1.81
    rCSI 2.86%
    PRS 94.93
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.7
    rCSI 4.14%
    PRS 82.91
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.7
    rCSI 6.12%
    PRS 83.25
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.68
    rCSI 2.83%
    PRS 85.02
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.68
    rCSI 2.97%
    PRS 95.97
  • blood vessel smooth muscle cell CL0019018
    CSI 1.66
    rCSI 13.48%
    PRS 93.03
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 1.63
    rCSI 9.11%
    PRS 95.19
  • tissue-resident macrophage CL0000864
    CSI 1.55
    rCSI 7.27%
    PRS 98.13
  • Hofbauer cell CL3000001
    CSI 1.49
    rCSI 2.82%
    PRS 97.1
  • stromal cell CL0000499
    CSI 1.38
    rCSI 3.88%
    PRS 91.17
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.26
    rCSI 2.23%
    PRS 84.39
  • retinal ganglion cell CL0000740
    CSI 1.18
    rCSI 2.61%
    PRS 86.41
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.67
    rCSI 2.09%
    PRS 85.92
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.62
    rCSI 2.36%
    PRS 85.1
  • central nervous system neuron CL2000029
    CSI 0.57
    rCSI 4.2%
    PRS 88.33
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.39
    rCSI 2.28%
    PRS 85.33
  • mesenchymal stem cell CL0000134
    CSI 0.26
    rCSI 2.81%
    PRS 95.38

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 **[ADAMTS2](/details-gene/9509)** (A Disintegrin and Metalloproteinase with Thrombospondin type 1 motif 2) is a protein-coding gene located on chromosome 5q35.3. It encodes a secreted zinc-dependent metalloendopeptidase that plays a crucial role in extracellular matrix (ECM) homeostasis. Specifically, [ADAMTS2](/details-gene/9509) functions as a procollagen N-proteinase, cleaving the N-terminal propeptides from procollagens type I, II, and III, which is an essential step for the correct assembly of collagen fibrils. Mutations in this gene are the cause of Ehlers-Danlos syndrome type VIIC ([225410](https://omim.org/entry/225410)), a connective tissue disorder characterized by extreme skin fragility and joint hypermobility [Link](https://doi.org/10.1086/302504). Expression data indicates its highest significance in mesenchymal-lineage cells responsible for ECM production and remodeling, particularly [hepatic stellate cell](/details-cell/CL0000632) and various lung fibroblasts. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of **[ADAMTS2](/details-gene/9509)** highlights its specialized function in tissue architecture and remodeling. The gene demonstrates the highest significance in cell types that actively synthesize and manage the extracellular matrix. The most prominent expression is observed in mesenchymal and fibroblast-like cells. It is a top marker for **[hepatic stellate cell](/details-cell/CL0000632)** (CSI: 16.04), which are key mediators of liver fibrosis, as well as **[alveolar type 1 fibroblast cell](/details-cell/CL4028004)** (CSI: 11.48) and **[fibroblast of lung](/details-cell/CL0002553)** (CSI: 6.01), underscoring its importance in lung tissue structure. High significance in **[mesodermal cell](/details-cell/CL0000222)** (CSI: 9.95) and **[mesenchymal cell](/details-cell/CL0008019)** (CSI: 3.43) is consistent with its fundamental role in the development and maintenance of connective tissues derived from the mesoderm. Interestingly, **[ADAMTS2](/details-gene/9509)** also shows notable significance in specific myeloid and adipose cell populations. Its expression in **[intermediate monocyte](/details-cell/CL0002393)** (CSI: 8.30) and resident tissue macrophages like **[Kupffer cell](/details-cell/CL0000091)** (CSI: 4.70) and **[lung macrophage](/details-cell/CL1001603)** (CSI: 3.75) suggests a potential role in immune-mediated tissue remodeling or wound healing processes. Furthermore, its activity in **[epicardial adipocyte](/details-cell/CL1000309)** (CSI: 5.12) and **[subcutaneous adipocyte](/details-cell/CL0002521)** (CSI: 3.64) may indicate a function in the development or maintenance of adipose tissue ECM. ## Pathways and Molecular Function The functional annotations for **[ADAMTS2](/details-gene/9509)** align precisely with its role as an ECM-modifying enzyme. Its primary molecular functions are **[Metalloendopeptidase activity](/details-gene/9509)** ([GO:0004222](https://www.ebi.ac.uk/QuickGO/term/GO:0004222)) and **[Zinc ion binding](/details-gene/9509)** ([GO:0008270](https://www.ebi.ac.uk/QuickGO/term/GO:0008270)), which are characteristic of its enzyme class. Biologically, it is integral to protein metabolism and connective tissue organization. Key involved biological processes include **[Collagen catabolic process](/details-gene/9509)** ([GO:0030574](https://www.ebi.ac.uk/QuickGO/term/GO:0030574)), **[Collagen fibril organization](/details-gene/9509)** ([GO:0030199](https://www.ebi.ac.uk/QuickGO/term/GO:0030199)), and the broader **[Extracellular matrix organization](/details-gene/9509)** ([GO:0030198](https://www.ebi.ac.uk/QuickGO/term/GO:0030198)). This is reinforced by its participation in Reactome pathways such as **[Collagen formation](/details-gene/9509)** ([R-HSA-1474290](https://reactome.org/content/detail/R-HSA-1474290)) and **[Extracellular matrix organization](/details-gene/9509)** ([R-HSA-1474244](https://reactome.org/content/detail/R-HSA-1474244)). Its involvement in developmental processes like **[Lung development](/details-gene/9509)** ([GO:0030324](https://www.ebi.ac.uk/QuickGO/term/GO:0030324)) and **[Skin development](/details-gene/9509)** ([GO:0043588](https://www.ebi.ac.uk/QuickGO/term/GO:0043588)) is consistent with its essential role in building the structural framework of these organs. Recent work has also shown it plays a role in regulating the activity of other ECM enzymes like lysyl oxidase [Link](https://doi.org/10.1074/jbc.ra119.007806). ## Research Directions The specific expression pattern and established enzymatic function of **[ADAMTS2](/details-gene/9509)** position it as a gene of interest in fibrotic diseases and tissue repair. **Testable Hypotheses:** 1. Given its exceptionally high significance in **[hepatic stellate cell](/details-cell/CL0000632)**, which are the primary drivers of liver fibrosis, it is hypothesized that the upregulation and enhanced enzymatic activity of **[ADAMTS2](/details-gene/9509)** in activated stellate cells are critical for the pathological deposition and maturation of collagen that characterizes liver cirrhosis. 2. Based on its high expression in **[alveolar type 1 fibroblast cell](/details-cell/CL4028004)** and its annotated role in lung development, it is hypothesized that dysregulation of **[ADAMTS2](/details-gene/9509)** activity contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF) by promoting aberrant collagen fibril assembly and tissue stiffening. **Proposed Experimental Approach:** To test the first hypothesis regarding liver fibrosis, a targeted approach could be employed. A conditional knockout mouse model could be generated to specifically delete *Adamts2* in hepatic stellate cells (e.g., using a Pdgfrb-Cre driver). These mice, along with wild-type controls, would be subjected to a model of liver fibrosis, such as carbon tetrachloride (CCl4) administration or bile duct ligation. The therapeutic effect of **[ADAMTS2](/details-gene/9509)** deletion would be assessed by quantifying collagen deposition (Sirius Red staining), measuring liver stiffness, and performing single-cell RNA sequencing to analyze changes in stellate cell activation states and the broader liver microenvironment. **Therapeutic Potential:** As an extracellular, secreted enzyme, **[ADAMTS2](/details-gene/9509)** is a highly druggable target. In the context of fibrotic diseases such as liver cirrhosis or IPF, where its activity is likely pathogenic, **[ADAMTS2](/details-gene/9509)** represents a promising target for **inhibition**. Therapeutic strategies could include the development of specific small molecule inhibitors that block its catalytic zinc-binding site or monoclonal antibodies that prevent substrate binding. Such inhibitors could potentially halt or reverse the progression of fibrosis by preventing the maturation and cross-linking of pathological collagen deposits.

Genular Protein ID: 1754856468

Symbol: ATS2_HUMAN

Name: A disintegrin and metalloproteinase with thrombospondin motifs 2

UniProtKB Accession Codes:

O95450

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 4 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 13 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 7 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10417273

Title: Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene.

PubMed ID: 10417273

DOI: 10.1086/302504

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 31152061

Title: Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain.

PubMed ID: 31152061

DOI: 10.1074/jbc.ra119.007806

Sequence Information:

  • Length: 1211
  • Mass: 134755
  • Checksum: 6C4F2C2D46A1F925
  • Sequence:
    • MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL GHGAERILAV 
PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG NEEEPGSHLF YNVTVFGRDL 
HLRLRPNARL VAPGATMEWQ GEKGTTRVEP LLGSCLYVGD VAGLAEASSV ALSNCDGLAG 
LIRMEEEEFF IEPLEKGLAA QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS 
RALGVLEEHA NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE 
IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ KPDTGHDEYH 
DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG 
QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR CSQQELSRYL HSYDCLLDDP FAHDWPALPQ 
LPGLHYSMNE QCRFDFGLGY MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA 
PGKHCFKGHC IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC 
SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD AKERCHLYCE 
SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD GVIGSSKQED KCGVCGGDNS 
HCKVVKGTFT RSPKKHGYIK MFEIPAGARH LLIQEVDATS HHLAVKNLET GKFILNEEND 
VDASSKTFIA MGVEWEYRDE DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS 
LNVDDNNVLE EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK 
PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT TRSVHAKHCN 
DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV LCRTADDSFG ICQEERPETA 
RTCRLGPCPR NISDPSKKSY VVQWLSRPDP DSPIRKISSK GHCQGDKSIF CRMEVLSRYC 
SIPGYNKLCC KSCNLYNNLT NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL 
EVPLNASSTN ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID 
EMRKKEMLGK F