ATS8_HUMAN
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 03-AUG-2022, entry version 187.
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}.
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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 STRING; 9606.ENSP00000257359; -.
DR MEROPS; M12.226; -.
DR GlyGen; Q9UP79; 5 sites.
DR iPTMnet; Q9UP79; -.
DR PhosphoSitePlus; Q9UP79; -.
DR BioMuta; ADAMTS8; -.
DR DMDM; 313104077; -.
DR MassIVE; Q9UP79; -.
DR PaxDb; Q9UP79; -.
DR PeptideAtlas; Q9UP79; -.
DR PRIDE; Q9UP79; -.
DR ProteomicsDB; 85356; -.
DR Antibodypedia; 33104; 210 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 CTD; 11095; -.
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; DSKPCVR; -.
DR OrthoDB; 125522at2759; -.
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; 8 hits in 1065 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 134 other tissues.
DR Genevisible; Q9UP79; HS.
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 Gene3D; 2.20.100.10; -; 2.
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; 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 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; PR01861; ADAMTS8.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00209; TSP1; 2.
DR SUPFAM; SSF82895; SSF82895; 2.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50092; TSP1; 2.
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; 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
