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

Gene ID: 9507, updated on 10-Dec-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
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Genomic context

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See ADAMTS4 in Genome Data Viewer
Location:
1q23.3
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (161184302..161199054, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (160321737..160336495, complement)
RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Elevated level of ADAMTS4 in plasma and peripheral monocytes from patients with acute coronary syndrome. Zha Y, et al. Clin Res Cardiol, 2010 Dec. PMID 20625753
  2. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. Bondeson J, et al. J Rheumatol, 2007 Mar. PMID 17295438
  3. Promotion of Tumor Growth by ADAMTS4 in Colorectal Cancer: Focused on Macrophages. Chen J, et al. Cell Physiol Biochem, 2018. PMID 29694979
  4. Relationship between ADAMTS4 and carotid atherosclerotic plaque vulnerability in humans. Dong H, et al. J Vasc Surg, 2018 Apr. PMID 29153440
  5. The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells. Corps AN, et al. Matrix Biol, 2008 Jun. PMID 18387286, Free PMC Article

See all (144) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. ADAMTS4 exacerbates lung cancer progression via regulating c-Myc protein stability and activating MAPK signaling pathway.
    Title: ADAMTS4 exacerbates lung cancer progression via regulating c-Myc protein stability and activating MAPK signaling pathway.
  2. miR-126a-5p inhibits H1N1-induced inflammation and matrix protease secretion in lung fibroblasts by targeting ADAMTS-4.
    Title: miR-126a-5p inhibits H1N1-induced inflammation and matrix protease secretion in lung fibroblasts by targeting ADAMTS-4.
  3. Amino-terminally elongated Abeta peptides are generated by the secreted metalloprotease ADAMTS4 and deposit in a subset of Alzheimer's disease brains.
    Title: Amino-terminally elongated Aβ peptides are generated by the secreted metalloprotease ADAMTS4 and deposit in a subset of Alzheimer's disease brains.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
    Title: The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
  9. 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.
  10. ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
    Title: ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
Submit: New GeneRIF Correction See all GeneRIFs (112)

Phenotypes

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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)

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_2024_08

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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