ATS4_BOVIN
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 03-AUG-2022, entry version 140.
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 PaxDb; Q9TT93; -.
DR PRIDE; Q9TT93; -.
DR GeneID; 286806; -.
DR KEGG; bta:286806; -.
DR CTD; 9507; -.
DR eggNOG; KOG3538; Eukaryota.
DR InParanoid; Q9TT93; -.
DR OrthoDB; 125522at2759; -.
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; ISS:AgBase.
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 Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 3.40.390.10; -; 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; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF17771; ADAM_CR_2; 1.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF01562; Pep_M12B_propep; 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; SSF82895; SSF82895; 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
