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UniProtKB/Swiss-Prot entry O75173


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ATS4_HUMAN
Primary accession number O75173
Secondary accession numbers Q5VTW2 Q6P4Q8 Q6UWA8 Q9UN83
Integrated into Swiss-Prot on December 1, 2000
Sequence was last modified on December 1, 2000 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 103)
Name and origin of the protein
Protein name A disintegrin and metalloproteinase with thrombospondin motifs 4 [Precursor]
Synonyms ADAMTS-4
ADAM-TS 4
ADAM-TS4
EC 3.4.24.82
Aggrecanase-1
ADMP-1
Gene name
Name: ADAMTS4
Synonyms: KIAA0688
ORFNames: UNQ769/PRO1563
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1126/science.284.5420.1664; PubMed=10356395 [NCBI, ExPASy, EBI, Israel, Japan]
Tortorella M.D., Burn T.C., Pratta M.A., Abbaszade I., Hollis J.M., Liu R.-Q., Rosenfeld S.A., Copeland R.A., Decicco C.P., Wynn R., Rockwell A., Yang F., Duke J.L., Solomon K., George H., Bruckner R., Nagase H., Itoh Y., Ellis D.M., Ross H., Wiswall B.H., Murphy K., Hillman M.C. Jr., Hollis G.F., Newton R.C., Magolda R.L., Trzaskos J.M., Arner E.C.;
"Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.";
Science 284:1664-1666(1999).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-626.
Sawaji Y., Nagase H., Saklatvala J., Clark A.R.;
"ADAMTS-4 genomic locus.";
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-77.
TISSUE=Brain;
DOI=10.1093/dnares/5.3.169; PubMed=9734811 [NCBI, ExPASy, EBI, Israel, Japan]
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. 5:169-176(1998).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
DOI=10.1101/gr.1293003; PubMed=12975309 [NCBI, ExPASy, EBI, Israel, Japan]
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-626.
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-4; ASN-304; VAL-369; THR-552; ALA-564 AND GLN-626.
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
DOI=10.1074/jbc.M001065200; PubMed=10827174 [NCBI, ExPASy, EBI, Israel, Japan]
Tortorella M.D., Pratta M.A., Liu R.-Q., Abbaszade I., Ross H., Burn T.C., Arner E.C.;
"The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage.";
J. Biol. Chem. 275:25791-25797(2000).
Comments
  • 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.
  • CATALYTIC ACTIVITY: Glutamyl endopeptidase; bonds cleaved include 370-Thr-Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan.
  • COFACTOR: Binds 1 zinc ion per subunit (By similarity).
  • SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (By similarity).
  • TISSUE SPECIFICITY: Expressed in brain, lung and heart. Expressed at very low level in placenta and skeletal muscles.
  • INDUCTION: By interleukin-1.
  • DOMAIN: The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
  • DOMAIN: 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.
  • PTM: The precursor is cleaved by a furin endopeptidase.
  • SIMILARITY: Contains 1 disintegrin domain.
  • SIMILARITY: Contains 1 peptidase M12B domain [view classification].
  • SIMILARITY: Contains 1 TSP type-1 domain.
  • CAUTION: Has sometimes been referred to as ADAMTS2.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF148213; AAD41494.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY044847; AAL02262.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB014588; BAA31663.2; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY358886; AAQ89245.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL590714; CAH72146.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC063293; AAH63293.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00307276; -.
PIR T00355; T00355.
RefSeq NP_005090.3; -.
UniGene Hs.211604
3D structure databases
PDB
2RJP; X-ray; 2.80 A; A/B/C/D=213-520.[ExPASy / RCSB / EBI]
3B2Z; X-ray; 2.80 A; A/B/C/D/E/F/G/H=213-520.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 2RJP; -.
3B2Z; -.
ModBase O75173.
Protein family/group databases
MEROPS M12.221; -.
Enzyme and pathway databases
BRENDA 3.4.24.82; 247.
Organism-specific databases
GeneCards GC01M159426; -.
H-InvDB HIX0001237; -.
HGNC HGNC:220; ADAMTS4.
GenAtlas ADAMTS4.
MIM 603876; gene. [NCBI / EBI]
PharmGKB PA24548; -.
HUGE KIAA0688.
Gene expression databases
ArrayExpress O75173; -.
Bgee O75173; -.
CleanEx HS_ADAMTS4; -.
GermOnline ENSG00000158859; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from direct assay from UniProtKB).
GO:0005578; Cellular component: proteinaceous extracellular matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0004222; Molecular function: metalloendopeptidase activity (inferred from electronic annotation from InterPro).
GO:0002020; Molecular function: protease binding (inferred from physical interaction from UniProtKB).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0006508; Biological process: proteolysis (traceable author statement from ProtInc).
GO:0001501; Biological process: skeletal system development (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR010294; ADAM_spacer1.
IPR018358; Disintegrin_CS.
IPR006025; Pept_M_Zn_BS.
IPR001590; Peptidase_M12B.
IPR013273; Peptidase_M12B_ADAM-TS.
IPR002870; Peptidase_M12B_N.
IPR000884; Thrombospondin_1_rpt.
Graphical view of domain structure.
Pfam PF05986; ADAM_spacer1; 1.
PF01562; Pep_M12B_propep; 1.
PF01421; Reprolysin; 1.
PF00090; TSP_1; 1.
Pfam graphical view of domain structure.
PRINTS PR01857; ADAMTSFAMILY.
SMART SM00209; TSP1; 1.
SMART graphical view of domain structure.
PROSITE PS50215; ADAM_MEPRO; 1.
PS00427; DISINTEGRIN_1; FALSE_NEG.
PS50214; DISINTEGRIN_2; FALSE_NEG.
PS50092; TSP1; 1.
PS00142; ZINC_PROTEASE; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE O75173; -.
Genome annotation databases
Ensembl ENSG00000158859; Homo sapiens. [Contig view]
GeneID 9507; -.
KEGG hsa:9507; -.
Phylogenomic databases
HOGENOM O75173; -.
HOVERGEN O75173; -.
Other
NextBio 35624; -.
PMAP-CutDB O75173; -.
SOURCE ADAMTS4; Homo sapiens.
ProtoNet O75173.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Cleavage on pair of basic residues; Direct protein sequencing; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism; Protease; Secreted; Signal; Zinc; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    51  51     Potential. 
PROPEP   52   212  161      PRO_0000029164
CHAIN   213   837  625     A disintegrin and metalloproteinase with thrombospondin motifs 4. PRO_0000029165
DOMAIN   218   428  211     Peptidase M12B. 
DOMAIN   437   519  83     Disintegrin. 
DOMAIN   520   575  56     TSP type-1. 
REGION   686   837  152     Spacer. 
MOTIF   192   199  8     Cysteine switch (By similarity). 
COMPBIAS   247   252  6     Poly-Ala. 
COMPBIAS   577   685  109     Cys-rich. 
ACT_SITE   362   362        By similarity. 
METAL   194   194        Zinc; in inhibited form (By similarity). 
METAL   361   361        Zinc; catalytic (By similarity). 
METAL   365   365        Zinc; catalytic (By similarity). 
METAL   371   371        Zinc; catalytic (By similarity). 
CARBOHYD   68    68        N-linked (GlcNAc...) (Potential). 
DISULFID   339   423        By similarity. 
DISULFID   377   407        By similarity. 
DISULFID   532   569        By similarity. 
DISULFID   536   574        By similarity. 
DISULFID   547   559        By similarity. 
VARIANT   4     4  1     T -> I (in dbSNP:rs17855814 [NCBI]). VAR_030636 
VARIANT   77    77  1     A -> T (in dbSNP:rs34448954 [NCBI]). VAR_057073 
VARIANT   304   304  1     D -> N (in dbSNP:rs17855813 [NCBI]). VAR_030637 
VARIANT   369   369  1     M -> V (in dbSNP:rs17855812 [NCBI]). VAR_030638 
VARIANT   552   552  1     P -> T (in dbSNP:rs17855815 [NCBI]). VAR_030639 
VARIANT   564   564  1     T -> A (in dbSNP:rs17855816 [NCBI]). VAR_030640 
VARIANT   626   626  1     R -> Q (in dbSNP:rs4233367 [NCBI]). VAR_022450 
VARIANT   836   836  1     R -> K (in dbSNP:rs11807350 [NCBI]). VAR_030641 
CONFLICT   306   306        D -> G (in Ref. 4; AAQ89245). 
CONFLICT   682   682        G -> R (in Ref. 2; AAL02262). 
STRAND   218   226  9      
HELIX   228   234  7      
HELIX   235   237  3      
HELIX   238   253  16      
HELIX   256   258  3      
STRAND   262   271  10      
STRAND   274   276  3      
HELIX   285   295  11      
HELIX   296   298  3      
STRAND   311   317  7      
TURN   322   324  3      
STRAND   328   333  6      
TURN   341   343  3      
STRAND   345   349  5      
HELIX   355   366  12      
HELIX   375   381  7      
STRAND   393   395  3      
HELIX   406   417  12      
TURN   418   423  6      
HELIX   439   442  4      
HELIX   445   453  9      
STRAND   463   465  3      
TURN   466   468  3      
STRAND   471   474  4      
STRAND   481   484  4      
STRAND   494   496  3      
STRAND   499   506  8      
Sequence information
Length: 837 AA [This is the length of the unprocessed precursor] Molecular weight: 90225 Da [This is the MW of the unprocessed precursor] CRC64: 5DF9C9AC137DF41F [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR LASPLPREEE 

        70         80         90        100        110        120 
IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEQDS GVQVEGLTVQ YLGQAPELLG 

       130        140        150        160        170        180 
GAEPGTYLTG TINGDPESVA SLHWDGGALL GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI 

       190        200        210        220        230        240 
LRRKSPASGQ GPMCNVKAPL GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR 

       250        260        270        280        290        300 
YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN 

       310        320        330        340        350        360 
TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAFTAA 

       370        380        390        400        410        420 
HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGY 

       430        440        450        460        470        480 
GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA 

       490        500        510        520        530        540 
MCQTKHSPWA DGTPCGPAQA CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV 

       550        560        570        580        590        600 
QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TEDCPTGSAL TFREEQCAAY NHRTDLFKSF 

       610        620        630        640        650        660 
PGPMDWVPRY TGVAPQDQCK LTCQARALGY YYVLEPRVVD GTPCSPDSSS VCVQGRCIHA 

       670        680        690        700        710        720 
GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN NVVTIPAGAT HILVRQQGNP 

       730        740        750        760        770        780 
GHRSIYLALK LPDGSYALNG EYTLMPSPTD VVLPGAVSLR YSGATAASET LSGHGPLAQP 

       790        800        810        820        830 
LTLQVLVAGN PQDTRLRYSF FVPRPTPSTP RPTPQDWLHR RAQILEILRR RPWAGRK 

O75173 in FASTA format

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