ID   ATS8_HUMAN              Reviewed;         889 AA.
AC   Q9UP79; Q9NZS0;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-NOV-2010, sequence version 2.
DT   27-MAR-2024, entry version 196.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 8;
DE            Short=ADAM-TS 8;
DE            Short=ADAM-TS8;
DE            Short=ADAMTS-8;
DE            EC=3.4.24.-;
DE   AltName: Full=METH-2;
DE   AltName: Full=METH-8;
DE   Flags: Precursor;
GN   Name=ADAMTS8; Synonyms=METH2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lung;
RX   PubMed=10438512; DOI=10.1074/jbc.274.33.23349;
RA   Vazquez F., Hastings G., Ortega M.-A., Lane T.F., Oikemus S., Lombardo M.,
RA   Iruela-Arispe M.L.;
RT   "METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new
RT   family of proteins with angio-inhibitory activity.";
RL   J. Biol. Chem. 274:23349-23357(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 194-439.
RX   PubMed=10610729; DOI=10.1006/geno.1999.6014;
RA   Georgiadis K.E., Hirohata S., Seldin M.F., Apte S.S.;
RT   "ADAM-TS8, a novel metalloprotease of the ADAM-TS family located on mouse
RT   chromosome 9 and human chromosome 11.";
RL   Genomics 62:312-315(1999).
CC   -!- FUNCTION: Has anti-angiogenic properties.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in adult and fetal lung, lower
CC       expression in brain, placenta, heart, stomach and fetal brain and
CC       kidney.
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. {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; AF060153; AAD48081.1; -; mRNA.
DR   EMBL; AP002986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF175283; AAF25806.1; -; mRNA.
DR   CCDS; CCDS41732.1; -.
DR   RefSeq; NP_008968.4; NM_007037.5.
DR   AlphaFoldDB; Q9UP79; -.
DR   SMR; Q9UP79; -.
DR   BioGRID; 116276; 2.
DR   IntAct; Q9UP79; 1.
DR   STRING; 9606.ENSP00000257359; -.
DR   MEROPS; M12.226; -.
DR   GlyCosmos; Q9UP79; 5 sites, No reported glycans.
DR   GlyGen; Q9UP79; 5 sites.
DR   iPTMnet; Q9UP79; -.
DR   PhosphoSitePlus; Q9UP79; -.
DR   BioMuta; ADAMTS8; -.
DR   DMDM; 313104077; -.
DR   MassIVE; Q9UP79; -.
DR   PaxDb; 9606-ENSP00000257359; -.
DR   PeptideAtlas; Q9UP79; -.
DR   ProteomicsDB; 85356; -.
DR   Antibodypedia; 33104; 226 antibodies from 25 providers.
DR   DNASU; 11095; -.
DR   Ensembl; ENST00000257359.7; ENSP00000257359.6; ENSG00000134917.10.
DR   GeneID; 11095; -.
DR   KEGG; hsa:11095; -.
DR   MANE-Select; ENST00000257359.7; ENSP00000257359.6; NM_007037.6; NP_008968.4.
DR   UCSC; uc001qgg.5; human.
DR   AGR; HGNC:224; -.
DR   DisGeNET; 11095; -.
DR   GeneCards; ADAMTS8; -.
DR   HGNC; HGNC:224; ADAMTS8.
DR   HPA; ENSG00000134917; Tissue enhanced (lung).
DR   MIM; 605175; gene.
DR   neXtProt; NX_Q9UP79; -.
DR   OpenTargets; ENSG00000134917; -.
DR   VEuPathDB; HostDB:ENSG00000134917; -.
DR   eggNOG; KOG3538; Eukaryota.
DR   GeneTree; ENSGT00940000159642; -.
DR   HOGENOM; CLU_000660_3_0_1; -.
DR   InParanoid; Q9UP79; -.
DR   OMA; EDTKPCG; -.
DR   OrthoDB; 2910701at2759; -.
DR   PhylomeDB; Q9UP79; -.
DR   TreeFam; TF331949; -.
DR   PathwayCommons; Q9UP79; -.
DR   Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR   Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR   BioGRID-ORCS; 11095; 9 hits in 1142 CRISPR screens.
DR   ChiTaRS; ADAMTS8; human.
DR   GeneWiki; ADAMTS8; -.
DR   GenomeRNAi; 11095; -.
DR   Pharos; Q9UP79; Tbio.
DR   PRO; PR:Q9UP79; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9UP79; Protein.
DR   Bgee; ENSG00000134917; Expressed in middle temporal gyrus and 136 other cell types or tissues.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR   GO; GO:0009673; F:low-affinity phosphate transmembrane transporter activity; TAS:ProtInc.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
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; -; 2.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 2.
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; IPR013277; Pept_M12B_ADAM-TS8.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR002870; Peptidase_M12B_N.
DR   InterPro; IPR000884; TSP1_rpt.
DR   InterPro; IPR036383; TSP1_rpt_sf.
DR   PANTHER; PTHR13723:SF41; A DISINTEGRIN AND METALLOPROTEINASE WITH THROMBOSPONDIN MOTIFS 8; 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; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF19030; TSP1_ADAMTS; 1.
DR   Pfam; PF00090; TSP_1; 1.
DR   PRINTS; PR01861; ADAMTS8.
DR   PRINTS; PR01857; ADAMTSFAMILY.
DR   SMART; SM00608; ACR; 1.
DR   SMART; SM00209; TSP1; 2.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF82895; TSP-1 type 1 repeat; 2.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50092; TSP1; 2.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; Q9UP79; HS.
PE   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Heparin-binding; Hydrolase; Metal-binding; Metalloprotease;
KW   Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..213
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000029178"
FT   CHAIN           214..889
FT                   /note="A disintegrin and metalloproteinase with
FT                   thrombospondin motifs 8"
FT                   /id="PRO_0000029179"
FT   DOMAIN          219..429
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          438..525
FT                   /note="Disintegrin"
FT   DOMAIN          526..581
FT                   /note="TSP type-1 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          833..888
FT                   /note="TSP type-1 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   REGION          138..210
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          690..831
FT                   /note="Spacer"
FT   COMPBIAS        169..184
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        364
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         363
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         367
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   BINDING         373
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        465
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        490
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        599
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        294..347
FT                   /evidence="ECO:0000250"
FT   DISULFID        323..329
FT                   /evidence="ECO:0000250"
FT   DISULFID        341..424
FT                   /evidence="ECO:0000250"
FT   DISULFID        379..408
FT                   /evidence="ECO:0000250"
FT   DISULFID        452..477
FT                   /evidence="ECO:0000250"
FT   DISULFID        463..486
FT                   /evidence="ECO:0000250"
FT   DISULFID        472..507
FT                   /evidence="ECO:0000250"
FT   DISULFID        501..512
FT                   /evidence="ECO:0000250"
FT   DISULFID        538..575
FT                   /evidence="ECO:0000250"
FT   DISULFID        542..580
FT                   /evidence="ECO:0000250"
FT   DISULFID        553..565
FT                   /evidence="ECO:0000250"
FT   CONFLICT        2
FT                   /note="L -> F (in Ref. 1; AAD48081)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        11..12
FT                   /note="PP -> LPF (in Ref. 1; AAD48081)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        194
FT                   /note="E -> R (in Ref. 3; AAF25806)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        412..439
FT                   /note="YLTELLDGGHGDCLLDAPAAALPLPTGL -> FSGCHLQGWIHFKYLCKCVS
FT                   ELKCDLMP (in Ref. 3; AAF25806)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        430
FT                   /note="A -> G (in Ref. 1; AAD48081)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        525
FT                   /note="A -> V (in Ref. 1; AAD48081)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   889 AA;  96460 MW;  E1767A6524BCEBAB CRC64;
     MLPAPAAPRW PPLLLLLLLL LPLARGAPAR PAAGGQASEL VVPTRLPGSA GELALHLSAF
     GKGFVLRLAP DDSFLAPEFK IERLGGSGRA TGGERGLRGC FFSGTVNGEP ESLAAVSLCR
     GLSGSFLLDG EEFTIQPQGA GGSLAQPHRL QRWGPAGARP LPRGPEWEVE TGEGQRQERG
     DHQEDSEEES QEEEAEGASE PPPPLGATSR TKRFVSEARF VETLLVADAS MAAFYGADLQ
     NHILTLMSVA ARIYKHPSIK NSINLMVVKV LIVEDEKWGP EVSDNGGLTL RNFCNWQRRF
     NQPSDRHPEH YDTAILLTRQ NFCGQEGLCD TLGVADIGTI CDPNKSCSVI EDEGLQAAHT
     LAHELGHVLS MPHDDSKPCT RLFGPMGKHH VMAPLFVHLN QTLPWSPCSA MYLTELLDGG
     HGDCLLDAPA AALPLPTGLP GRMALYQLDQ QCRQIFGPDF RHCPNTSAQD VCAQLWCHTD
     GAEPLCHTKN GSLPWADGTP CGPGHLCSEG SCLPEEEVER PKPVADGGWA PWGPWGECSR
     TCGGGVQFSH RECKDPEPQN GGRYCLGRRA KYQSCHTEEC PPDGKSFREQ QCEKYNAYNY
     TDMDGNLLQW VPKYAGVSPR DRCKLFCRAR GRSEFKVFEA KVIDGTLCGP ETLAICVRGQ
     CVKAGCDHVV DSPRKLDKCG VCGGKGNSCR KVSGSLTPTN YGYNDIVTIP AGATNIDVKQ
     RSHPGVQNDG NYLALKTADG QYLLNGNLAI SAIEQDILVK GTILKYSGSI ATLERLQSFR
     PLPEPLTVQL LTVPGEVFPP KVKYTFFVPN DVDFSMQSSK ERATTNIIQP LLHAQWVLGD
     WSECSSTCGA GWQRRTVECR DPSGQASATC NKALKPEDAK PCESQLCPL
//