ATS4_RAT
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 03-AUG-2022, entry version 143.
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, 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 -!- 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.
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 STRING; 10116.ENSRNOP00000004713; -.
DR ChEMBL; CHEMBL4523453; -.
DR MEROPS; M12.221; -.
DR GlyGen; Q9ESP7; 2 sites.
DR PaxDb; Q9ESP7; -.
DR GeneID; 66015; -.
DR KEGG; rno:66015; -.
DR UCSC; RGD:621242; rat.
DR CTD; 9507; -.
DR RGD; 621242; Adamts4.
DR eggNOG; KOG3538; Eukaryota.
DR InParanoid; Q9ESP7; -.
DR OrthoDB; 125522at2759; -.
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:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISO:RGD.
DR GO; GO:0008237; F:metallopeptidase activity; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0002020; F:protease 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:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0044691; P:tooth eruption; IEP:RGD.
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; 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; 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 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
