| IED ID | IndEnz0002013707 |
| Enzyme Type ID | protease013707 |
| Protein Name |
A disintegrin and metalloproteinase with thrombospondin motifs 4 ADAM-TS 4 ADAM-TS4 ADAMTS-4 EC 3.4.24.82 ADMP-1 Aggrecanase-1 |
| Gene Name | ADAMTS4 KIAA0688 UNQ769/PRO1563 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLASLLPSARLASPLPREEEIVFPEKLNGSVLPGSGAPARLLCRLQAFGETLLLELEQDSGVQVEGLTVQYLGQAPELLGGAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAELHLQPLEGGTPNSAGGPGAHILRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSRFVETLVVADDKMAAFHGAGLKRYLLTVMAAAAKAFKHPSIRNPVSLVVTRLVILGSGEEGPQVGPSAAQTLRSFCAWQRGLNTPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMADVGTVCDPARSCAIVEDDGLQSAFTAAHELGHVFNMLHDNSKPCISLNGPLSTSRHVMAPVMAHVDPEEPWSPCSARFITDFLDNGYGHCLLDKPEAPLHLPVTFPGKDYDADRQCQLTFGPDSRHCPQLPPPCAALWCSGHLNGHAMCQTKHSPWADGTPCGPAQACMGGRCLHMDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGVQFSSRDCTRPVPRNGGKYCEGRRTRFRSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSFPGPMDWVPRYTGVAPQDQCKLTCQAQALGYYYVLEPRVVDGTPCSPDSSSVCVQGRCIHAGCDRIIGSKKKFDKCMVCGGDGSGCSKQSGSFRKFRYGYNNVVTIPAGATHILVRQQGNPGHRSIYLALKLPDGSYALNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQPLTLQVLVAGNPQDTRLRYSFFVPRPTPSTPRPTPQDWLHRRAQILEILRRRPWAGRK |
| Enzyme Length | 837 |
| Uniprot Accession Number | O75173 |
| Absorption | |
| Active Site | ACT_SITE 362; /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, ECO:0000255|PROSITE-ProRule:PRU10095, ECO:0000269|PubMed:18042673" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Glutamyl endopeptidase. Bonds cleaved include 370-Thr-Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan.; EC=3.4.24.82; |
| DNA Binding | |
| EC Number | 3.4.24.82 |
| Enzyme Function | 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. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (1); Beta strand (15); Chain (1); Disulfide bond (11); Domain (3); Erroneous initiation (1); Frameshift (1); Glycosylation (1); Helix (10); Metal binding (4); Motif (1); Natural variant (8); Propeptide (1); Region (1); Sequence conflict (2); Signal peptide (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Cleavage on pair of basic residues;Direct protein sequencing;Disulfide bond;Extracellular matrix;Glycoprotein;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal;Zinc;Zymogen |
| Interact With | |
| Induction | INDUCTION: By IL1/interleukin-1. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: The precursor is cleaved by a furin endopeptidase.; PTM: 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). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..51; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 2RJP; 3B2Z; 4WK7; 4WKE; 4WKI; |
| Mapped Pubmed ID | 10438522; 10751421; 10986281; 11067851; 11796708; 11801682; 11831030; 11854269; 11956193; 12054629; 12202483; 12514189; 12646579; 14561220; 14662755; 14701864; 14715656; 14744861; 15161923; 15296936; 16003758; 16099106; 16133547; 16464858; 16507336; 16677612; 16741450; 16771712; 17009305; 17095512; 17208315; 17265492; 17295438; 17311924; 17430884; 17470431; 17606262; 17978660; 18039650; 18050214; 18156631; 18221525; 18387286; 18660489; 18671934; 18720094; 18941754; 19054571; 19342688; 19643179; 19796186; 19944557; 20625753; 20664926; 20857147; 21334453; 21345877; 21664283; 21946608; 21988832; 22065068; 22324945; 22562232; 22588082; 22735305; 23082219; 23137648; 23295731; 23319426; 23406982; 23438438; 23859810; 23889335; 24051360; 24126638; 24474687; 24732836; 24786121; 25225099; 25415648; 25433723; 25477257; 25501175; 25544610; 25592103; 25707877; 25709087; 26152337; 26495885; 26916548; 27182768; 27401455; 27706574; 28005267; 28081267; 28099917; 28323982; 28829887; 28888475; 28955046; 29135310; 29153440; 29694979; 30016600; 30187439; 30369484; 30426203; 30730845; 31734379; 32067610; 32490633; 33116313; 33350314; 33358865; 33444494; |
| Motif | MOTIF 192..199; /note=Cysteine switch; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 90,197 |
| Kinetics | |
| Metal Binding | METAL 194; /note=Zinc; in inhibited form; /evidence=ECO:0000250; METAL 361; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:18042673; METAL 365; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:18042673; METAL 371; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:18042673 |
| Rhea ID | |
| Cross Reference Brenda |