ID   ATS4_RAT                Reviewed;         630 AA.
AC   Q9ESP7; Q9ESP6; Q9ESP8;
DT   05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   05-DEC-2001, sequence version 2.
DT   04-NOV-2026, entry version 156.
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=Aggrecanase-1;
DE   Flags: Precursor; Fragment;
GN   Name=Adamts4;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar; TISSUE=Brain;
RX   PubMed=10961658; DOI=10.1016/s0304-3940(00)01285-4;
RA   Satoh K., Suzuki N., Yokota H.;
RT   "ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)
RT   is transcriptionally induced in beta-amyloid treated rat astrocytes.";
RL   Neurosci. Lett. 289:177-180(2000).
CC   -!- FUNCTION: Cleaves aggrecan, a cartilage proteoglycan, at the '392-
CC       Glu-|-Ala-393' site and may be involved in its turnover. Also cleaves
CC       COMP. May play an important role in the destruction of aggrecan in
CC       arthritic diseases. {ECO:0000250|UniProtKB:O75173}.
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   -!- TISSUE SPECIFICITY: Brain specific.
CC   -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC       a tight interaction with the extracellular matrix. The spacer domain is
CC       also required for cleavage of COMP (By similarity).
CC       {ECO:0000250|UniProtKB:O75173}.
CC   -!- PTM: The precursor is cleaved by a furin endopeptidase.
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}.
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DR   EMBL; AB042272; BAB16474.1; -; mRNA.
DR   EMBL; AB042271; BAB16473.1; -; mRNA.
DR   EMBL; AB042273; BAB16475.1; -; mRNA.
DR   RefSeq; NP_076449.1; NM_023959.1.
DR   AlphaFoldDB; Q9ESP7; -.
DR   SMR; Q9ESP7; -.
DR   FunCoup; Q9ESP7; 64.
DR   STRING; 10116.ENSRNOP00000004713; -.
DR   ChEMBL; CHEMBL4523453; -.
DR   MEROPS; M12.221; -.
DR   GlyCosmos; Q9ESP7; 2 sites, No reported glycans.
DR   GlyGen; Q9ESP7; 2 sites.
DR   PhosphoSitePlus; Q9ESP7; -.
DR   PaxDb; 10116-ENSRNOP00000004713; -.
DR   GeneID; 66015; -.
DR   KEGG; rno:66015; -.
DR   UCSC; RGD:621242; rat.
DR   AGR; RGD:621242; -.
DR   CTD; 9507; -.
DR   RGD; 621242; Adamts4.
DR   eggNOG; KOG3538; Eukaryota.
DR   InParanoid; Q9ESP7; -.
DR   OMA; AACCHLM; -.
DR   OrthoDB; 12257at9989; -.
DR   PhylomeDB; Q9ESP7; -.
DR   BRENDA; 3.4.24.82; 5301.
DR   Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-RNO-5173214; O-glycosylation of TSR domain-containing proteins.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0016607; C:nuclear speck; ISO:RGD.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISO:RGD.
DR   GO; GO:0008237; F:metallopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR   GO; GO:0002020; F:protease binding; ISO:RGD.
DR   GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0030167; P:proteoglycan catabolic process; ISO:RGD.
DR   GO; GO:0006508; P:proteolysis; ISO:RGD.
DR   CDD; cd04273; ZnMc_ADAMTS_like; 1.
DR   FunFam; 2.20.100.10:FF:000006; A disintegrin and metalloproteinase with thrombospondin motifs 1; 1.
DR   FunFam; 2.60.120.830:FF:000001; A disintegrin and metalloproteinase with thrombospondin motifs 1; 1.
DR   FunFam; 3.40.1620.60:FF:000003; A disintegrin and metalloproteinase with thrombospondin motifs 1; 1.
DR   FunFam; 3.40.390.10:FF:000001; A disintegrin and metalloproteinase with thrombospondin motifs 1; 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; IPR050439; 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   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW   Reference proteome; Secreted; Zinc; Zymogen.
FT   PROPEP          <1..5
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000029168"
FT   CHAIN           6..630
FT                   /note="A disintegrin and metalloproteinase with
FT                   thrombospondin motifs 4"
FT                   /id="PRO_0000029169"
FT   DOMAIN          11..221
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          233..303
FT                   /note="Disintegrin"
FT   DOMAIN          313..368
FT                   /note="TSP type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   REGION          479..630
FT                   /note="Spacer"
FT   ACT_SITE        155
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         154
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         158
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   BINDING         164
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        474
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        86..138
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        115..120
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        132..216
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        170..200
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        242..265
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        253..275
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        260..294
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        288..299
FT                   /evidence="ECO:0000250|UniProtKB:O75173"
FT   DISULFID        325..362
FT                   /evidence="ECO:0000250"
FT   DISULFID        329..367
FT                   /evidence="ECO:0000250"
FT   DISULFID        340..352
FT                   /evidence="ECO:0000250"
FT   NON_TER         1
SQ   SEQUENCE   630 AA;  68385 MW;  63A428753167C7EF CRC64;
     RRTKRFASLS RFVETLVVAD DKMAAFHGAG LKHYLLTVMA AAAKAFKHPS IRNPVNLVVT
     RLVILGSGQE VPQVGPSAAQ TLRSFCTWQK GLNPPNDSDP DHFDTAILFT RQDLCGVSTC
     DALGMAGVGT VCDPARSCAI VEDDGLQSAF TAAHELGHVF NMLHDNSKPC ANLNGQGSSS
     RHVMAPVMAH VDPEEPWSPC SARFITDFLD NGYGHCLLDK PEAPLHLPVT FPGKDYDADR
     QCQLTFGPDS SHCPQLPPPC AALWCFGHLN GHAMCQTKHS PWADGTPCGP AQACMGGRCL
     HVDQLKDFNI PQAGGWGPWG PWGDCSRTCG GGVQFSSRDC TKPVPRNGGK YCEGRRTPFR
     SCNTKNCPHG SALTFREEQC AAYNHRTDLF KSFPGPMDWV PRYTGVAPRD QCKLTCQARA
     LGYYYVLEPR VADGTPCSPD SSSVCVQGRC IHAGCDRIIG SKKKFDKCMV CGGNGSSCSK
     QSGSFKKFRY GYSDVVTIPA GRTHILVRQQ GGSGLKSIYL ALKLADGSYA LNGEYTLMPS
     STDVVLPGAV SLRYSGRTAA SETLSGHGPL AQPLTLQVLV AGNPQNVRLR YSFFVPRPVP
     STPRPPPQNW LQRRAEILEI LRKRTWAGRK
//