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    ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif 4 [ Homo sapiens (human) ]

    Gene ID: 9507, updated on 31-Mar-2024

    Summary

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    Official Symbol
    ADAMTS4provided by HGNC
    Official Full Name
    ADAM metallopeptidase with thrombospondin type 1 motif 4provided by HGNC
    Primary source
    HGNC:HGNC:220
    See related
    Ensembl:ENSG00000158859 MIM:603876; AllianceGenome:HGNC:220
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ADMP-1; ADAMTS-2; ADAMTS-4
    Summary
    This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene lacks a C-terminal TS motif. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The expression of this gene is upregulated in arthritic disease and this may contribute to disease progression through the degradation of aggrecan. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
    Expression
    Broad expression in gall bladder (RPKM 12.3), appendix (RPKM 11.7) and 19 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    1q23.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (161184302..161199054, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (160321737..160336495, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (161154092..161168844, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1470 Neighboring gene ubiquitin specific peptidase 21 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161137271-161137934 Neighboring gene protoporphyrinogen oxidase Neighboring gene beta-1,4-galactosyltransferase 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1471 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:161146985-161147484 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161148623-161149124 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1982 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1983 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161162728-161163541 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1474 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1984 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161166678-161167583 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161170109-161170830 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1985 Neighboring gene NADH:ubiquinone oxidoreductase core subunit S2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:161187006-161187992 Neighboring gene Fc epsilon receptor Ig Neighboring gene apolipoprotein A2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-κB-SIRT-1 pathway. Aswani SS, et al. Physiol Int, 2023 Jun 12. PMID 37216221
    2. Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries. Khanam R, et al. Sci Rep, 2022 Jun 14. PMID 35701493, Free PMC Article
    3. The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities. Novak R, et al. J Vasc Res, 2022. PMID 35051931
    4. Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts. Cilek MZ, et al. Lab Invest, 2022 Jan. PMID 34718343
    5. Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4). Miura K, et al. Biochim Biophys Acta Gen Subj, 2021 Mar. PMID 33358865

    See all (138) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.
      Title: ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.
    2. Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-kappaB-SIRT-1 pathway.
      Title: Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-κB-SIRT-1 pathway.
    3. ADAMTS4 is involved in the production of the Alzheimer disease amyloid biomarker APP669-711.
      Title: ADAMTS4 is involved in the production of the Alzheimer disease amyloid biomarker APP669-711.
    4. Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries.
      Title: Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries.
    5. The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
      Title: The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
    6. Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts.
      Title: Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts.
    7. ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
      Title: ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
    8. Interrelationship of Osteopontin, MMP-9 and ADAMTS4 in Patients With Osteoarthritis Undergoing Total Joint Arthroplasty.
      Title: Interrelationship of Osteopontin, MMP-9 and ADAMTS4 in Patients With Osteoarthritis Undergoing Total Joint Arthroplasty.
    9. The utility of synovial fluid levels of ADAMTS9 and ADAMTS4 in predicting treatment responses to intraarticular steroid injections in patients with knee osteoarthritis
      Title: The utility of synovial fluid levels of ADAMTS9 and ADAMTS4 in predicting treatment responses to intraarticular steroid injections in patients with knee osteoarthritis.
    10. Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4).
      Title: Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4).
    Submit: New GeneRIF Correction See all GeneRIFs (109)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0688

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables metallopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables peptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in extracellular matrix disassembly TAS
    Traceable Author Statement
    more info
    		  
    involved_in extracellular matrix organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in collagen-containing extracellular matrix HDA PubMed 
    is_active_in extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    A disintegrin and metalloproteinase with thrombospondin motifs 4
    Names
    ADAM-TS 4
    ADAM-TS4
    a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4
    aggrecanase-1
    epididymis secretory sperm binding protein
    NP_001307265.1
    NP_005090.3
    XP_047290860.1
    XP_054195683.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001320336.3 → NP_001307265.1  A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as ADAMTS4_v1) uses an alternate splice site in the 3' coding region resulting in a frameshift compared to variant 1. The encoded isoform (2) has a longer and distinct C-terminus compared to isoform 1, but may undergo proteolytic processing similar to isoform 1.
      Source sequence(s)
      AA603151, AB014588, AF148213, AL590714, AY358886, BC063293, DA098917, DQ364570
      UniProtKB/TrEMBL
      A8K6A8
      Conserved Domains (5) summary
      smart00209
      Location:531 → 575
      TSP1; Thrombospondin type 1 repeats
      cd04273
      Location:218 → 425
      ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...
      pfam01421
      Location:218 → 428
      Reprolysin; Reprolysin (M12B) family zinc metalloprotease
      pfam01562
      Location:70 → 181
      Pep_M12B_propep; Reprolysin family propeptide
      cl15456
      Location:438 → 509
      ADAM_CR; ADAM cysteine-rich

    2. NM_005099.6 → NP_005090.3  A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_005090.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the shorter isoform (1).
      Source sequence(s)
      AA603151, AB014588, AF148213, AL590714, AY358886, BC063293, DA098917
      Consensus CDS
      CCDS1223.1
      UniProtKB/Swiss-Prot
      O75173, Q2HYD0, Q5VTW2, Q6P4Q8, Q6UWA8, Q9UN83
      UniProtKB/TrEMBL
      A8K6A8
      Related
      ENSP00000356975.4, ENST00000367996.6
      Conserved Domains (6) summary
      smart00209
      Location:531 → 575
      TSP1; Thrombospondin type 1 repeats
      cd04273
      Location:218 → 425
      ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...
      pfam01421
      Location:218 → 428
      Reprolysin; Reprolysin (M12B) family zinc metalloprotease
      pfam01562
      Location:70 → 181
      Pep_M12B_propep; Reprolysin family propeptide
      pfam05986
      Location:687 → 802
      ADAM_spacer1; ADAM-TS Spacer 1
      cl15456
      Location:438 → 509
      ADAM_CR; ADAM cysteine-rich

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      161184302..161199054 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047434904.1 → XP_047290860.1  A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      160321737..160336495 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339708.1 → XP_054195683.1  A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75173.3 GenPept UniProtKB/Swiss-Prot:O75173

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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