A disintegrin and metalloproteinase with thrombospondin motifs 4

Details

Name
A disintegrin and metalloproteinase with thrombospondin motifs 4
Synonyms
  • 3.4.24.82
  • ADAM-TS 4
  • ADMP-1
  • Aggrecanase-1
  • KIAA0688
Gene Name
ADAMTS4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008538|A disintegrin and metalloproteinase with thrombospondin motifs 4
MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLASLLPSARLASPLPREEE
IVFPEKLNGSVLPGSGAPARLLCRLQAFGETLLLELEQDSGVQVEGLTVQYLGQAPELLG
GAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAELHLQPLEGGTPNSAGGPGAHI
LRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSRFVETLVVADDKMAAFHGAGLKR
YLLTVMAAAAKAFKHPSIRNPVSLVVTRLVILGSGEEGPQVGPSAAQTLRSFCAWQRGLN
TPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMADVGTVCDPARSCAIVEDDGLQSAFTAA
HELGHVFNMLHDNSKPCISLNGPLSTSRHVMAPVMAHVDPEEPWSPCSARFITDFLDNGY
GHCLLDKPEAPLHLPVTFPGKDYDADRQCQLTFGPDSRHCPQLPPPCAALWCSGHLNGHA
MCQTKHSPWADGTPCGPAQACMGGRCLHMDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGV
QFSSRDCTRPVPRNGGKYCEGRRTRFRSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSF
PGPMDWVPRYTGVAPQDQCKLTCQAQALGYYYVLEPRVVDGTPCSPDSSSVCVQGRCIHA
GCDRIIGSKKKFDKCMVCGGDGSGCSKQSGSFRKFRYGYNNVVTIPAGATHILVRQQGNP
GHRSIYLALKLPDGSYALNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQP
LTLQVLVAGNPQDTRLRYSFFVPRPTPSTPRPTPQDWLHRRAQILEILRRRPWAGRK
Number of residues
837
Molecular Weight
90196.02
Theoretical pI
Not Available
GO Classification
Functions
metalloendopeptidase activity / metallopeptidase activity / peptidase activity / protease binding / zinc ion binding
Processes
defense response to bacterium / extracellular matrix disassembly / extracellular matrix organization / proteolysis / skeletal system development
Components
extracellular matrix / extracellular region / extracellular space / proteinaceous extracellular matrix
General Function
Zinc ion binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0013261|A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4)
ATGTCCCAGACAGGCTCGCATCCCGGGAGGGGCTTGGCAGGGCGCTGGCTGTGGGGAGCC
CAACCCTGCCTCCTGCTCCCCATTGTGCCGCTCTCCTGGCTGGTGTGGCTGCTTCTGCTA
CTGCTGGCCTCTCTCCTGCCCTCAGCCCGGCTGGCCAGCCCCCTCCCCCGGGAGGAGGAG
ATCGTGTTTCCAGAGAAGCTCAACGGCAGCGTCCTGCCTGGCTCGGGCGCCCCTGCCAGG
CTGTTGTGCCGCTTGCAGGCCTTTGGGGAGACGCTGCTACTAGAGCTGGAGCAGGACTCC
GGTGTGCAGGTCGAGGGGCTGACAGTGCAGTACCTGGGCCAGGCGCCTGAGCTGCTGGGT
GGAGCAGAGCCTGGCACCTACCTGACTGGCACCATCAATGGAGATCCGGAGTCGGTGGCA
TCTCTGCACTGGGATGGGGGAGCCCTGTTAGGCGTGTTACAATATCGGGGGGCTGAACTC
CACCTCCAGCCCCTGGAGGGAGGCACCCCTAACTCTGCTGGGGGACCTGGGGCTCACATC
CTACGCCGGAAGAGTCCTGCCAGCGGTCAAGGTCCCATGTGCAACGTCAAGGCTCCTCTT
GGAAGCCCCAGCCCCAGACCCCGAAGAGCCAAGCGCTTTGCTTCACTGAGTAGATTTGTG
GAGACACTGGTGGTGGCAGATGACAAGATGGCCGCATTCCACGGTGCGGGGCTAAAGCGC
TACCTGCTAACAGTGATGGCAGCAGCAGCCAAGGCCTTCAAGCACCCAAGCATCCGCAAT
CCTGTCAGCTTGGTGGTGACTCGGCTAGTGATCCTGGGGTCAGGCGAGGAGGGGCCCCAA
GTGGGGCCCAGTGCTGCCCAGACCCTGCGCAGCTTCTGTGCCTGGCAGCGGGGCCTCAAC
ACCCCTGAGGACTCGGACCCTGACCACTTTGACACAGCCATTCTGTTTACCCGTCAGGAC
CTGTGTGGAGTCTCCACTTGCGACACGCTGGGTATGGCTGATGTGGGCACCGTCTGTGAC
CCGGCTCGGAGCTGTGCCATTGTGGAGGATGATGGGCTCCAGTCAGCCTTCACTGCTGCT
CATGAACTGGGTCATGTCTTCAACATGCTCCATGACAACTCCAAGCCATGCATCAGTTTG
AATGGGCCTTTGAGCACCTCTCGCCATGTCATGGCCCCTGTGATGGCTCATGTGGATCCT
GAGGAGCCCTGGTCCCCCTGCAGTGCCCGCTTCATCACTGACTTCCTGGACAATGGCTAT
GGGCACTGTCTCTTAGACAAACCAGAGGCTCCATTGCATCTGCCTGTGACTTTCCCTGGC
AAGGACTATGATGCTGACCGCCAGTGCCAGCTGACCTTCGGGCCCGACTCACGCCATTGT
CCACAGCTGCCGCCGCCCTGTGCTGCCCTCTGGTGCTCTGGCCACCTCAATGGCCATGCC
ATGTGCCAGACCAAACACTCGCCCTGGGCCGATGGCACACCCTGCGGGCCCGCACAGGCC
TGCATGGGTGGTCGCTGCCTCCACATGGACCAGCTCCAGGACTTCAATATTCCACAGGCT
GGTGGCTGGGGTCCTTGGGGACCATGGGGTGACTGCTCTCGGACCTGTGGGGGTGGTGTC
CAGTTCTCCTCCCGAGACTGCACGAGGCCTGTCCCCCGGAATGGTGGCAAGTACTGTGAG
GGCCGCCGTACCCGCTTCCGCTCCTGCAACACTGAGGACTGCCCAACTGGCTCAGCCCTG
ACCTTCCGCGAGGAGCAGTGTGCTGCCTACAACCACCGCACCGACCTCTTCAAGAGCTTC
CCAGGGCCCATGGACTGGGTTCCTCGCTACACAGGCGTGGCCCCCCAGGACCAGTGCAAA
CTCACCTGCCAGGCCCAGGCACTGGGCTACTACTATGTGCTGGAGCCACGGGTGGTAGAT
GGGACCCCCTGTTCCCCGGACAGCTCCTCGGTCTGTGTCCAGGGCCGATGCATCCATGCT
GGCTGTGATCGCATCATTGGCTCCAAGAAGAAGTTTGACAAGTGCATGGTGTGCGGAGGG
GACGGTTCTGGTTGCAGCAAGCAGTCAGGCTCCTTCAGGAAATTCAGGTACGGATACAAC
AATGTGGTCACTATCCCCGCGGGGGCCACCCACATTCTTGTCCGGCAGCAGGGAAACCCT
GGCCACCGGAGCATCTACTTGGCCCTGAAGCTGCCAGATGGCTCCTATGCCCTCAATGGT
GAATACACGCTGATGCCCTCCCCCACAGATGTGGTACTGCCTGGGGCAGTCAGCTTGCGC
TACAGCGGGGCCACTGCAGCCTCAGAGACACTGTCAGGCCATGGGCCACTGGCCCAGCCT
TTGACACTGCAAGTCCTAGTGGCTGGCAACCCCCAGGACACACGCCTCCGATACAGCTTC
TTCGTGCCCCGGCCGACCCCTTCAACGCCACGCCCCACTCCCCAGGACTGGCTGCACCGA
AGAGCACAGATTCTGGAGATCCTTCGGCGGCGCCCCTGGGCGGGCAGGAAATAA
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO75173
UniProtKB Entry NameATS4_HUMAN
HGNC IDHGNC:220
General References
  1. Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R, Rosenfeld SA, Copeland RA, Decicco CP, Wynn R, Rockwell A, Yang F, Duke JL, Solomon K, George H, Bruckner R, Nagase H, Itoh Y, Ellis DM, Ross H, Wiswall BH, Murphy K, Hillman MC Jr, Hollis GF, Newton RC, Magolda RL, Trzaskos JM, Arner EC: Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science. 1999 Jun 4;284(5420):1664-6. [PubMed:10356395]
  2. Wainwright SD, Bondeson J, Hughes CE: An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. Matrix Biol. 2006 Jul;25(5):317-20. Epub 2006 Apr 6. [PubMed:16723216]
  3. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1998 Jun 30;5(3):169-76. [PubMed:9734811]
  4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309]
  5. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Tortorella M, Pratta M, Liu RQ, Abbaszade I, Ross H, Burn T, Arner E: The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. J Biol Chem. 2000 Aug 18;275(33):25791-7. [PubMed:10827174]
  8. Royer-Zemmour B, Ponsole-Lenfant M, Gara H, Roll P, Leveque C, Massacrier A, Ferracci G, Cillario J, Robaglia-Schlupp A, Vincentelli R, Cau P, Szepetowski P: Epileptic and developmental disorders of the speech cortex: ligand/receptor interaction of wild-type and mutant SRPX2 with the plasminogen activator receptor uPAR. Hum Mol Genet. 2008 Dec 1;17(23):3617-30. doi: 10.1093/hmg/ddn256. Epub 2008 Aug 21. [PubMed:18718938]
  9. Wainwright SD, Bondeson J, Caterson B, Hughes CE: ADAMTS-4_v1 is a splice variant of ADAMTS-4 that is expressed as a protein in human synovium and cleaves aggrecan at the interglobular domain. Arthritis Rheum. 2013 Nov;65(11):2866-75. doi: 10.1002/art.38102. [PubMed:23897278]
  10. Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W: Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5. Protein Sci. 2008 Jan;17(1):16-21. Epub 2007 Nov 27. [PubMed:18042673]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06822TinzaparinapprovedunknowninhibitorDetails