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Aliases for ADAMTS4 Gene

Aliases for ADAMTS4 Gene

  • ADAM Metallopeptidase With Thrombospondin Type 1 Motif, 4 2 3
  • A Disintegrin-Like And Metalloprotease (Reprolysin Type) With Thrombospondin Type 1 Motif, 4 2 3
  • Aggrecanase-1 3 4
  • EC 4 64
  • ADAM-TS 4 3 4
  • ADAM-TS4 3 4
  • ADAMTS-4 3 4
  • ADMP-1 3 4
  • A Disintegrin And Metalloproteinase With Thrombospondin Motifs 4 3
  • EC 3.4.24 64
  • ADAMTS-2 3
  • KIAA0688 4

External Ids for ADAMTS4 Gene

Summaries for ADAMTS4 Gene

Entrez Gene Summary for ADAMTS4 Gene

  • This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the 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. It is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The cleavage of aggrecan and brevican suggests key roles of this enzyme in arthritic disease and in the central nervous system, potentially, in the progression of glioma. [provided by RefSeq, Jul 2008]

GeneCards Summary for ADAMTS4 Gene

ADAMTS4 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif, 4) is a Protein Coding gene. Among its related pathways are Endochondral Ossification and Degradation of the extracellular matrix. GO annotations related to this gene include metalloendopeptidase activity and peptidase activity. An important paralog of this gene is ADAMTS16.

UniProtKB/Swiss-Prot for ADAMTS4 Gene

  • Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the 392-Glu- -Ala-393 site

Gene Wiki entry for ADAMTS4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ADAMTS4 Gene

Genomics for ADAMTS4 Gene

Genomic Location for ADAMTS4 Gene

161,184,308 bp from pter
161,199,056 bp from pter
14,749 bases
Minus strand

Genomic View for ADAMTS4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ADAMTS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ADAMTS4 Gene

Regulatory Elements for ADAMTS4 Gene

Proteins for ADAMTS4 Gene

  • Protein details for ADAMTS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 4
    Protein Accession:
    Secondary Accessions:
    • Q2HYD0
    • Q5VTW2
    • Q6P4Q8
    • Q6UWA8
    • Q9UN83

    Protein attributes for ADAMTS4 Gene

    837 amino acids
    Molecular mass:
    90197 Da
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.;
    Quaternary structure:
    • Interacts with SRPX2.
    • Sequence=BAA31663.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ADAMTS4 Gene

    Alternative splice isoforms for ADAMTS4 Gene


neXtProt entry for ADAMTS4 Gene

Proteomics data for ADAMTS4 Gene at MOPED

Post-translational modifications for ADAMTS4 Gene

  • Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).
  • The precursor is cleaved by a furin endopeptidase
  • Glycosylation at Asn68

Other Protein References for ADAMTS4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for ADAMTS4 Gene

Gene Families for ADAMTS4 Gene

  • ADAMTS :ADAM metallopeptidases with thrombospondin type 1 motif


  • The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix:
    • O75173
  • The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme:
    • O75173
  • Contains 1 disintegrin domain.:
    • O75173
  • Contains 1 peptidase M12B domain.:
    • O75173
  • Contains 1 TSP type-1 domain.:
    • O75173
genes like me logo Genes that share domains with ADAMTS4: view

Function for ADAMTS4 Gene

Molecular function for ADAMTS4 Gene

GENATLAS Biochemistry: a disintegrin-like and metalloprotease domain (reprolysin type),aggrecanase 1,with thrombospondin type 1 motif 4,potentially degrading aggrecan in arthritis disease,extracellular matrix protein
UniProtKB/Swiss-Prot CatalyticActivity: Glutamyl endopeptidase; bonds cleaved include 370-Thr-Glu-Gly-Glu- -Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan
UniProtKB/Swiss-Prot Function: Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the 392-Glu- -Ala-393 site
UniProtKB/Swiss-Prot Induction: By IL1/interleukin-1

Enzyme Numbers (IUBMB) for ADAMTS4 Gene

Gene Ontology (GO) - Molecular Function for ADAMTS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 14744861
GO:0004222 metalloendopeptidase activity IEA --
GO:0005515 protein binding IPI 18718938
GO:0008233 peptidase activity TAS 10751421
GO:0008237 metallopeptidase activity TAS 10356395
genes like me logo Genes that share ontologies with ADAMTS4: view
genes like me logo Genes that share phenotypes with ADAMTS4: view

Animal Models for ADAMTS4 Gene

MGI Knock Outs for ADAMTS4:

miRNA for ADAMTS4 Gene

miRTarBase miRNAs that target ADAMTS4

No data available for Transcription Factor Targeting and HOMER Transcription for ADAMTS4 Gene

Localization for ADAMTS4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ADAMTS4 Gene

Secreted, extracellular space, extracellular matrix.

Subcellular locations from

Jensen Localization Image for ADAMTS4 Gene COMPARTMENTS Subcellular localization image for ADAMTS4 gene
Compartment Confidence
extracellular 4
plasma membrane 2
cytosol 1
endoplasmic reticulum 1
golgi apparatus 1
lysosome 1

Gene Ontology (GO) - Cellular Components for ADAMTS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005578 proteinaceous extracellular matrix IEA --
GO:0005615 extracellular space IDA 14744861
GO:0031012 extracellular matrix IDA 23658023
genes like me logo Genes that share ontologies with ADAMTS4: view

Pathways for ADAMTS4 Gene

genes like me logo Genes that share pathways with ADAMTS4: view

Pathways by source for ADAMTS4 Gene

1 Sino Biological pathway for ADAMTS4 Gene
1 BioSystems pathway for ADAMTS4 Gene

Gene Ontology (GO) - Biological Process for ADAMTS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development TAS 10356395
GO:0006508 proteolysis IEA --
GO:0022617 extracellular matrix disassembly TAS --
GO:0030198 extracellular matrix organization TAS --
GO:0042742 defense response to bacterium IEA --
genes like me logo Genes that share ontologies with ADAMTS4: view

Compounds for ADAMTS4 Gene

(7) Novoseek inferred chemical compound relationships for ADAMTS4 Gene

Compound -log(P) Hits PubMed IDs
glycosaminoglycan 67.3 6
chondroitin sulfate 50.3 10
glucosamine 36.2 1
pge2 32.2 4
tgf beta1 30.9 2
genes like me logo Genes that share compounds with ADAMTS4: view

Transcripts for ADAMTS4 Gene

mRNA/cDNA for ADAMTS4 Gene

Unigene Clusters for ADAMTS4 Gene

ADAM metallopeptidase with thrombospondin type 1 motif, 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ADAMTS4 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b
SP1: - -

Relevant External Links for ADAMTS4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ADAMTS4 Gene

mRNA expression in normal human tissues for ADAMTS4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ADAMTS4 Gene

This gene is overexpressed in Ovary (5.7) and Adipose - Visceral (Omentum) (5.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for ADAMTS4 Gene

SOURCE GeneReport for Unigene cluster for ADAMTS4 Gene Hs.211604

mRNA Expression by UniProt/SwissProt for ADAMTS4 Gene

Tissue specificity: Expressed in brain, lung and heart. Expressed at very low level in placenta and skeletal muscles. Isoform 2 is detected in osteoarthritic synovium.
genes like me logo Genes that share expressions with ADAMTS4: view

Orthologs for ADAMTS4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ADAMTS4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ADAMTS4 36
  • 99.72 (n)
  • 99.64 (a)
  • 100 (a)
(Bos Taurus)
Mammalia ADAMTS4 36
  • 89.25 (n)
  • 91.76 (a)
  • 91 (a)
(Canis familiaris)
Mammalia ADAMTS4 36
  • 87.34 (n)
  • 91.76 (a)
  • 78 (a)
(Mus musculus)
Mammalia Adamts4 36
  • 86.82 (n)
  • 90.38 (a)
Adamts4 16
Adamts4 37
  • 90 (a)
(Monodelphis domestica)
Mammalia ADAMTS4 37
  • 85 (a)
(Rattus norvegicus)
Mammalia Adamts4 36
  • 86.14 (n)
  • 88.53 (a)
(Anolis carolinensis)
Reptilia ADAMTS4 37
  • 63 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia adamts4 36
  • 66.32 (n)
  • 68.05 (a)
Species with no ortholog for ADAMTS4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for ADAMTS4 Gene

Gene Tree for ADAMTS4 (if available)
Gene Tree for ADAMTS4 (if available)

Paralogs for ADAMTS4 Gene

Selected SIMAP similar genes for ADAMTS4 Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with ADAMTS4: view

Variants for ADAMTS4 Gene

Sequence variations from dbSNP and Humsavar for ADAMTS4 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs3813622 -- 161,193,843(+) CAGAA(A/C/G/T)GGAAG intron-variant
rs7512012 -- 161,192,383(+) GTGCC(A/G)GCCAC intron-variant
rs12404950 -- 161,190,768(+) GGTCA(A/G)GTTCC utr-variant-3-prime
rs12738103 -- 161,192,879(+) TATAA(G/T)TTGAC intron-variant
rs17855815 - 161,193,721(+) CCGGG(G/T)GACAG missense, reference

Structural Variations from Database of Genomic Variants (DGV) for ADAMTS4 Gene

Variant ID Type Subtype PubMed ID
esv32799 CNV Gain 17666407

Relevant External Links for ADAMTS4 Gene

HapMap Linkage Disequilibrium report

Disorders for ADAMTS4 Gene

(2) University of Copenhagen DISEASES for ADAMTS4 Gene

(11) Novoseek inferred disease relationships for ADAMTS4 Gene

Disease -log(P) Hits PubMed IDs
osteoarthritis 77.5 13
arthritis 53.6 6
chondrosarcoma 41.4 2
necrosis 33.1 4
rheumatoid arthritis 29.7 4

Relevant External Links for ADAMTS4

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with ADAMTS4: view

No data available for UniProtKB/Swiss-Prot for ADAMTS4 Gene

Publications for ADAMTS4 Gene

  1. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. (PMID: 10356395) Tortorella M.D. … Arner E.C. (Science 1999) 3 4 23
  2. The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. (PMID: 10827174) Tortorella M.D. … Arner E.C. (J. Biol. Chem. 2000) 3 4 23
  3. An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. (PMID: 16723216) Wainwright S.D. … Hughes C.E. (Matrix Biol. 2006) 3 4 23
  4. Expression of ADAMTS-4 (aggrecanase-1) and possible involvement in regression of lumbar disc herniation. (PMID: 16741450) Hatano E. … Matsumoto T. (Spine 2006) 3 23
  5. ADAMTS4 (aggrecanase-1) cleaves human brain versican V2 at Glu405-Gln406 to generate glial hyaluronate binding protein. (PMID: 14561220) Westling J. … Sandy J.D. (Biochem. J. 2004) 3 23

Products for ADAMTS4 Gene

Sources for ADAMTS4 Gene

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