ID   ATS4_BOVIN              Reviewed;         839 AA.
AC   Q9TT93; A6QLR5; Q7YS95;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2006, sequence version 3.
DT   24-JAN-2024, entry version 145.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 4;
DE            Short=ADAM-TS 4;
DE            Short=ADAM-TS4;
DE            Short=ADAMTS-4;
DE            EC=3.4.24.82;
DE   AltName: Full=ADMP-1;
DE   AltName: Full=Aggrecanase-1;
DE   Flags: Precursor;
GN   Name=ADAMTS4;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Arai M., Anderson D., Annis B., Collins-Racie L., Corcoran C.,
RA   DiBlasio-Smith E., Morris E., Dorner A., LaVallie E.;
RT   "Cloning and characterization of bovine aggrecanase-1.";
RL   Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 332-531.
RC   TISSUE=Cartilage;
RX   PubMed=10403768; DOI=10.1006/bbrc.1999.0909;
RA   Flannery C.R., Little C.B., Hughes C.E., Caterson B.;
RT   "Expression of ADAMTS homologues in articular cartilage.";
RL   Biochem. Biophys. Res. Commun. 260:318-322(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 332-531.
RC   TISSUE=Cartilage chondrocyte;
RX   PubMed=10625599; DOI=10.1074/jbc.275.2.721;
RA   Curtis C.L., Hughes C.E., Flannery C.R., Little C.B., Harwood J.L.,
RA   Caterson B.;
RT   "n-3 fatty acids specifically modulate catabolic factors involved in
RT   articular cartilage degradation.";
RL   J. Biol. Chem. 275:721-724(2000).
RN   [5]
RP   PROTEIN SEQUENCE OF 213-239; 610-615 AND 626-637.
RC   TISSUE=Cartilage;
RX   PubMed=10356395; DOI=10.1126/science.284.5420.1664;
RA   Tortorella M.D., Burn T.C., Pratta M.A., Abbaszade I., Hollis J.M.,
RA   Liu R.-Q., Rosenfeld S.A., Copeland R.A., Decicco C.P., Wynn R.,
RA   Rockwell A., Yang F., Duke J.L., Solomon K., George H., Bruckner R.,
RA   Nagase H., Itoh Y., Ellis D.M., Ross H., Wiswall B.H., Murphy K.,
RA   Hillman M.C. Jr., Hollis G.F., Newton R.C., Magolda R.L., Trzaskos J.M.,
RA   Arner E.C.;
RT   "Purification and cloning of aggrecanase-1: a member of the ADAMTS family
RT   of proteins.";
RL   Science 284:1664-1666(1999).
CC   -!- FUNCTION: Cleaves aggrecan, a cartilage proteoglycan, and may be
CC       involved in its turnover. May play an important role in the destruction
CC       of aggrecan in arthritic diseases. Cleaves aggrecan at the '392-Glu-|-
CC       Ala-393' site.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Glutamyl endopeptidase. Bonds cleaved include 370-Thr-Glu-Gly-
CC         Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian
CC         aggrecan.; EC=3.4.24.82;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:O75173};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O75173};
CC   -!- SUBUNIT: Interacts with SRPX2. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- INDUCTION: By interleukin-1.
CC   -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC       a tight interaction with the extracellular matrix.
CC   -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC       binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC       dissociation of the cysteine from the zinc ion upon the activation-
CC       peptide release activates the enzyme.
CC   -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
CC   -!- PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a
CC       threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-
CC       G of the TSP type-1 repeat domains where C1 and C2 are the first and
CC       second cysteine residue of the repeat, respectively. Fucosylated
CC       repeats can then be further glycosylated by the addition of a beta-1,3-
CC       glucose residue by the glucosyltransferase, B3GALTL. Fucosylation
CC       mediates the efficient secretion of ADAMTS family members. Can also be
CC       C-glycosylated with one or two mannose molecules on tryptophan residues
CC       within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated.
CC       These other glycosylations can also facilitate secretion (By
CC       similarity). {ECO:0000250}.
CC   -!- CAUTION: Has sometimes been referred to as ADAMTS2. {ECO:0000305}.
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DR   EMBL; AF516915; AAP47196.1; -; mRNA.
DR   EMBL; BC148059; AAI48060.1; -; mRNA.
DR   EMBL; AF192770; AAF07176.1; -; mRNA.
DR   RefSeq; NP_858053.1; NM_181667.1.
DR   AlphaFoldDB; Q9TT93; -.
DR   SMR; Q9TT93; -.
DR   STRING; 9913.ENSBTAP00000017583; -.
DR   ChEMBL; CHEMBL3874; -.
DR   MEROPS; M12.221; -.
DR   GlyCosmos; Q9TT93; 1 site, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000017583; -.
DR   GeneID; 286806; -.
DR   KEGG; bta:286806; -.
DR   CTD; 9507; -.
DR   eggNOG; KOG3538; Eukaryota.
DR   InParanoid; Q9TT93; -.
DR   OrthoDB; 2910701at2759; -.
DR   PRO; PR:Q9TT93; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd04273; ZnMc_ADAMTS_like; 1.
DR   Gene3D; 2.60.120.830; -; 1.
DR   Gene3D; 3.40.1620.60; -; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 1.
DR   InterPro; IPR006586; ADAM_Cys-rich.
DR   InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR   InterPro; IPR041645; ADAMTS_CR_2.
DR   InterPro; IPR045371; ADAMTS_CR_3.
DR   InterPro; IPR010294; ADAMTS_spacer1.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   PANTHER; PTHR13723:SF38; A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIFS 4; 1.
DR   PANTHER; PTHR13723; ADAMTS A DISINTEGRIN AND METALLOPROTEASE WITH THROMBOSPONDIN MOTIFS PROTEASE; 1.
DR   Pfam; PF17771; ADAMTS_CR_2; 1.
DR   Pfam; PF19236; ADAMTS_CR_3; 1.
DR   Pfam; PF05986; ADAMTS_spacer1; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF00090; TSP_1; 1.
DR   PRINTS; PR01857; ADAMTSFAMILY.
DR   SMART; SM00608; ACR; 1.
DR   SMART; SM00209; TSP1; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50092; TSP1; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase;
KW   Metal-binding; Metalloprotease; Protease; Reference proteome; Secreted;
KW   Signal; Zinc; Zymogen.
FT   SIGNAL          1..51
FT                   /evidence="ECO:0000255"
FT   PROPEP          52..212
FT                   /evidence="ECO:0000269|PubMed:10356395"
FT                   /id="PRO_0000239802"
FT   CHAIN           213..839
FT                   /note="A disintegrin and metalloproteinase with
FT                   thrombospondin motifs 4"
FT                   /id="PRO_0000078209"
FT   DOMAIN          218..428
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          437..519
FT                   /note="Disintegrin"
FT   DOMAIN          520..575
FT                   /note="TSP type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   REGION          166..209
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          686..839
FT                   /note="Spacer"
FT                   /evidence="ECO:0000250"
FT   MOTIF           192..199
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        362
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         194
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /note="in inhibited form"
FT                   /evidence="ECO:0000250"
FT   BINDING         361
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         365
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         371
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   CARBOHYD        68
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        293..345
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        322..327
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        339..423
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        377..407
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        449..472
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        460..482
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        467..501
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        495..506
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        532..569
FT                   /evidence="ECO:0000250"
FT   DISULFID        536..574
FT                   /evidence="ECO:0000250"
FT   DISULFID        547..559
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   839 AA;  90280 MW;  1B488A27DF5B96B1 CRC64;
     MSHMDSHPGR GLADGWLWGI QPRLLLPTVP VSGSRLVWLL LLASLLPSAW PASPLPREEE
     IVFPEKLNGS VLPGLGAPAR LLYRLPAFGE TLLLELEKDP GVQVEGLTVQ YLGRAPELLG
     GAEPGTYLTG TINGDPESVA SLHWDGGALL GVLQYRGTEL HIQPLEGGAP NSAGGPGAHI
     LRRKSPVSGQ GPMCNVKAPP GKPSPSPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR
     YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV VLGPGEEGPQ VGPSAAQTLR SFCAWQRGLN
     TPDDADPGHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAFTAA
     HELGHVFSML HDNSKQCTGL NGPESTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGF
     GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA
     MCQTKHSPWA DGTPCGPAQA CMGGRCLHVD QLQAFNVPQA GGWGPWGSWG DCSRSCGGGV
     QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TQDCPTGSAL TFREEQCAAY NHRTDLFKNF
     PGPMDWVPRY TGVAPRDQCK LTCQTRALGY YYVLDPRVAD GTPCSPDSSS VCVQGRCIHA
     GCDRVIGSKK KFDKCMVCGG DGSSCSKQSG SFKKFRYGYN NVVTIPAGAT HILVRQQGSP
     SVRSLYLALK LPDGSYALNG EYTLIPSPTD VVLPGAVSLR YSGATAASET LSGHGPLAEP
     LTLQVLVAGN PQNARLRYSF FVPRPRPVPS TPRPTPQDWL RRKSQILEIL RRRSWAGRK
//