ATS4_PONAB
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 03-AUG-2022, entry version 85.
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}.
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DR EMBL; CR857094; CAH89399.1; -; mRNA.
DR AlphaFoldDB; Q5RFQ8; -.
DR SMR; Q5RFQ8; -.
DR STRING; 9601.ENSPPYP00000000708; -.
DR MEROPS; M12.221; -.
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: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 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 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
