ID ATS4_PONAB Reviewed; 837 AA. AC Q5RFQ8; DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 24-JAN-2024, entry version 88. 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; GN Name=ADAMTS4; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. 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 -!- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CR857094; CAH89399.1; -; mRNA. DR AlphaFoldDB; Q5RFQ8; -. DR SMR; Q5RFQ8; -. DR STRING; 9601.ENSPPYP00000000708; -. DR MEROPS; M12.221; -. DR GlyCosmos; Q5RFQ8; 1 site, No reported glycans. DR eggNOG; KOG3538; Eukaryota. DR InParanoid; Q5RFQ8; -. DR Proteomes; UP000001595; Unplaced. 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; IEA:InterPro. DR GO; GO:0008237; F:metallopeptidase activity; ISS:UniProtKB. DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; IEA:InterPro. 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 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; Signal; Zinc; Zymogen. FT SIGNAL 1..51 FT /evidence="ECO:0000255" FT PROPEP 52..212 FT /evidence="ECO:0000250" FT /id="PRO_0000239803" FT CHAIN 213..837 FT /note="A disintegrin and metalloproteinase with FT thrombospondin motifs 4" FT /id="PRO_0000239804" 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..191 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 686..837 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 837 AA; 90262 MW; 08F5E69F65CF6B4C CRC64; MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR LASPLPREEE IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEHDS GVQVEGLTVQ YLGQAPELLG GAEPGTYLTG TINGEPESVA SLHWDGGALL GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI LRRKSPASGQ GPMCNVKAPL GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAYTAA HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGY GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA MCQTKHSPWA DGTPCGPAQA CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TEDCPTGSVL TFREEQCAAY NHCTDLFKSF PGPMDWVPRY TGVAPQDQCK LTCQARALGY YYVLEPRVVD GTPCSPDSSS VCVQGRCIHA GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN NVVTIPTGAT HILVRQQGNP GHRSIYLALK LPDGSYALNG EYTLMPSPTD VVLPGAISLR YSGATAASET LSGHGPLAQP LTLQVLVAGN PQDARLRYSF FVPRPTPSTP HPTPQDWLHR RAQILEILRR RPWVGRK //