ATS7_HUMAN
ID ATS7_HUMAN Reviewed; 1686 AA.
AC Q9UKP4; Q14F51; Q6P7J9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 7;
DE Short=ADAM-TS 7;
DE Short=ADAM-TS7;
DE Short=ADAMTS-7;
DE EC=3.4.24.-;
DE AltName: Full=COMPase;
DE Flags: Precursor;
GN Name=ADAMTS7;
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], FUNCTION, COFACTOR, PH DEPENDENCE, INTERACTION
RP WITH COMP, INDUCTION, TISSUE SPECIFICITY, AND VARIANTS ALA-1319; SER-1414
RP AND ALA-1583.
RX PubMed=16585064; DOI=10.1096/fj.05-3877fje;
RA Liu C.-J., Kong W., Ilalov K., Yu S., Xu K., Prazak L., Fajardo M.,
RA Sehgal B., Di Cesare P.E.;
RT "ADAMTS-7: a metalloproteinase that directly binds to and degrades
RT cartilage oligomeric matrix protein.";
RL FASEB J. 20:988-990(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-307.
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10464288; DOI=10.1074/jbc.274.36.25555;
RA Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S.;
RT "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc
RT metalloproteases.";
RL J. Biol. Chem. 274:25555-25563(1999).
RN [4]
RP PROTEIN SEQUENCE OF 237-243, IDENTIFICATION, GLYCOSYLATION, PROTEOLYTIC
RP PROCESSING, AND TISSUE SPECIFICITY.
RX PubMed=15192113; DOI=10.1074/jbc.m402380200;
RA Somerville R.P.T., Longpre J.-M., Apel E.D., Lewis R.M., Wang L.W.,
RA Sanes J.R., Leduc R., Apte S.S.;
RT "ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin
RT sulfate proteoglycan containing a mucin domain.";
RL J. Biol. Chem. 279:35159-35175(2004).
CC -!- FUNCTION: Metalloprotease that may play a role in the degradation of
CC COMP. {ECO:0000269|PubMed:16585064}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is between 7.5 and 9.5. {ECO:0000269|PubMed:16585064};
CC -!- SUBUNIT: Interacts with COMP. {ECO:0000269|PubMed:16585064}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}. Note=Also found associated with the external cell
CC surface. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney and pancreas. Detected in meniscus, bone,
CC tendon, cartilage, synovium, fat and ligaments.
CC {ECO:0000269|PubMed:15192113, ECO:0000269|PubMed:16585064}.
CC -!- INDUCTION: Up-regulated in articular cartilage and synovium from
CC arthritis patients. {ECO:0000269|PubMed:16585064}.
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: N-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. N- and C-
CC glycosylations can also facilitate secretion. O-glycosylated
CC proteoglycan. Contains chondroitin sulfate.
CC {ECO:0000269|PubMed:15192113}.
CC -!- PTM: May be cleaved by a furin endopeptidase (By similarity). The
CC precursor is sequentially processed. {ECO:0000250,
CC ECO:0000269|PubMed:15192113}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD56358.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AY327122; AAQ94616.1; -; mRNA.
DR EMBL; BC061631; AAH61631.1; -; mRNA.
DR EMBL; AF140675; AAD56358.1; ALT_SEQ; mRNA.
DR CCDS; CCDS32303.1; -.
DR RefSeq; NP_055087.2; NM_014272.4.
DR AlphaFoldDB; Q9UKP4; -.
DR SMR; Q9UKP4; -.
DR BioGRID; 116344; 101.
DR IntAct; Q9UKP4; 4.
DR STRING; 9606.ENSP00000373472; -.
DR MEROPS; M12.231; -.
DR GlyGen; Q9UKP4; 17 sites, 2 O-linked glycans (14 sites).
DR iPTMnet; Q9UKP4; -.
DR PhosphoSitePlus; Q9UKP4; -.
DR BioMuta; ADAMTS7; -.
DR DMDM; 205371741; -.
DR EPD; Q9UKP4; -.
DR MassIVE; Q9UKP4; -.
DR PaxDb; Q9UKP4; -.
DR PeptideAtlas; Q9UKP4; -.
DR PRIDE; Q9UKP4; -.
DR ProteomicsDB; 84828; -.
DR Antibodypedia; 27710; 187 antibodies from 21 providers.
DR DNASU; 11173; -.
DR Ensembl; ENST00000388820.5; ENSP00000373472.4; ENSG00000136378.15.
DR GeneID; 11173; -.
DR KEGG; hsa:11173; -.
DR MANE-Select; ENST00000388820.5; ENSP00000373472.4; NM_014272.5; NP_055087.2.
DR UCSC; uc002bej.4; human.
DR CTD; 11173; -.
DR DisGeNET; 11173; -.
DR GeneCards; ADAMTS7; -.
DR HGNC; HGNC:223; ADAMTS7.
DR HPA; ENSG00000136378; Tissue enhanced (heart).
DR MIM; 605009; gene.
DR neXtProt; NX_Q9UKP4; -.
DR OpenTargets; ENSG00000136378; -.
DR PharmGKB; PA24551; -.
DR VEuPathDB; HostDB:ENSG00000136378; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000159819; -.
DR HOGENOM; CLU_000660_2_1_1; -.
DR InParanoid; Q9UKP4; -.
DR OMA; VDEGHCD; -.
DR OrthoDB; 125522at2759; -.
DR PhylomeDB; Q9UKP4; -.
DR TreeFam; TF313537; -.
DR PathwayCommons; Q9UKP4; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q9UKP4; -.
DR BioGRID-ORCS; 11173; 14 hits in 1070 CRISPR screens.
DR ChiTaRS; ADAMTS7; human.
DR GenomeRNAi; 11173; -.
DR Pharos; Q9UKP4; Tbio.
DR PRO; PR:Q9UKP4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9UKP4; protein.
DR Bgee; ENSG00000136378; Expressed in right atrium auricular region and 86 other tissues.
DR Genevisible; Q9UKP4; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
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; IDA:BHF-UCL.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IDA:BHF-UCL.
DR GO; GO:0071347; P:cellular response to interleukin-1; IMP:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:BHF-UCL.
DR GO; GO:0043931; P:ossification involved in bone maturation; IEA:Ensembl.
DR GO; GO:0006029; P:proteoglycan metabolic process; IEA:Ensembl.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP:BHF-UCL.
DR Gene3D; 2.20.100.10; -; 8.
DR Gene3D; 3.40.390.10; -; 1.
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; IPR010909; PLAC.
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; SM00209; TSP1; 8.
DR SUPFAM; SSF82895; SSF82895; 8.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 7.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Proteoglycan; Reference proteome;
KW Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..236
FT /evidence="ECO:0000269|PubMed:15192113"
FT /id="PRO_0000029176"
FT CHAIN 237..1686
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 7"
FT /id="PRO_0000029177"
FT DOMAIN 242..452
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 462..537
FT /note="Disintegrin"
FT DOMAIN 538..593
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 821..880
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 881..940
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 942..995
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1411..1459
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1462..1522
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1523..1567
FT /note="TSP type-1 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1569..1629
FT /note="TSP type-1 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1632..1672
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 698..809
FT /note="Spacer"
FT REGION 1024..1043
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1080..1257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1344..1396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1666..1686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 202..209
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 1098..1112
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1134..1149
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1178..1201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1213..1229
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1242..1257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1364..1391
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 204
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 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 693
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 778
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 318..372
FT /evidence="ECO:0000250"
FT DISULFID 347..354
FT /evidence="ECO:0000250"
FT DISULFID 366..447
FT /evidence="ECO:0000250"
FT DISULFID 405..431
FT /evidence="ECO:0000250"
FT DISULFID 474..497
FT /evidence="ECO:0000250"
FT DISULFID 485..503
FT /evidence="ECO:0000250"
FT DISULFID 492..522
FT /evidence="ECO:0000250"
FT DISULFID 516..527
FT /evidence="ECO:0000250"
FT DISULFID 550..587
FT /evidence="ECO:0000250"
FT DISULFID 554..592
FT /evidence="ECO:0000250"
FT DISULFID 565..577
FT /evidence="ECO:0000250"
FT VARIANT 214
FT /note="S -> P (in dbSNP:rs3825807)"
FT /id="VAR_046112"
FT VARIANT 307
FT /note="T -> M (in dbSNP:rs2127898)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_046113"
FT VARIANT 1319
FT /note="T -> A (in dbSNP:rs11630236)"
FT /evidence="ECO:0000269|PubMed:16585064"
FT /id="VAR_046114"
FT VARIANT 1414
FT /note="G -> S (in dbSNP:rs2929155)"
FT /evidence="ECO:0000269|PubMed:16585064"
FT /id="VAR_046115"
FT VARIANT 1583
FT /note="G -> A (in dbSNP:rs7495616)"
FT /evidence="ECO:0000269|PubMed:16585064"
FT /id="VAR_046116"
FT CONFLICT 642
FT /note="E -> K (in Ref. 1; AAD56358)"
FT /evidence="ECO:0000305"
FT CONFLICT 1101
FT /note="H -> R (in Ref. 2; AAQ94616)"
FT /evidence="ECO:0000305"
FT CONFLICT 1364
FT /note="S -> T (in Ref. 2; AAQ94616)"
FT /evidence="ECO:0000305"
FT CONFLICT 1479
FT /note="G -> D (in Ref. 2; AAQ94616)"
FT /evidence="ECO:0000305"
FT CONFLICT 1511
FT /note="P -> H (in Ref. 2; AAQ94616)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1686 AA; 184095 MW; AB38264B8E8DB740 CRC64;
MPGGPSPRSP APLLRPLLLL LCALAPGAPG PAPGRATEGR AALDIVHPVR VDAGGSFLSY
ELWPRALRKR DVSVRRDAPA FYELQYRGRE LRFNLTANQH LLAPGFVSET RRRGGLGRAH
IRAHTPACHL LGEVQDPELE GGLAAISACD GLKGVFQLSN EDYFIEPLDS APARPGHAQP
HVVYKRQAPE RLAQRGDSSA PSTCGVQVYP ELESRRERWE QRQQWRRPRL RRLHQRSVSK
EKWVETLVVA DAKMVEYHGQ PQVESYVLTI MNMVAGLFHD PSIGNPIHIT IVRLVLLEDE
EEDLKITHHA DNTLKSFCKW QKSINMKGDA HPLHHDTAIL LTRKDLCAAM NRPCETLGLS
HVAGMCQPHR SCSINEDTGL PLAFTVAHEL GHSFGIQHDG SGNDCEPVGK RPFIMSPQLL
YDAAPLTWSR CSRQYITRFL DRGWGLCLDD PPAKDIIDFP SVPPGVLYDV SHQCRLQYGA
YSAFCEDMDN VCHTLWCSVG TTCHSKLDAA VDGTRCGENK WCLSGECVPV GFRPEAVDGG
WSGWSAWSIC SRSCGMGVQS AERQCTQPTP KYKGRYCVGE RKRFRLCNLQ ACPAGRPSFR
HVQCSHFDAM LYKGQLHTWV PVVNDVNPCE LHCRPANEYF AEKLRDAVVD GTPCYQVRAS
RDLCINGICK NVGCDFEIDS GAMEDRCGVC HGNGSTCHTV SGTFEEAEGL GYVDVGLIPA
GAREIRIQEV AEAANFLALR SEDPEKYFLN GGWTIQWNGD YQVAGTTFTY ARRGNWENLT
SPGPTKEPVW IQLLFQESNP GVHYEYTIHR EAGGHDEVPP PVFSWHYGPW TKCTVTCGRG
VQRQNVYCLE RQAGPVDEEH CDPLGRPDDQ QRKCSEQPCP ARWWAGEWQL CSSSCGPGGL
SRRAVLCIRS VGLDEQSALE PPACEHLPRP PTETPCNRHV PCPATWAVGN WSQCSVTCGE
GTQRRNVLCT NDTGVPCDEA QQPASEVTCS LPLCRWPLGT LGPEGSGSGS SSHELFNEAD
FIPHHLAPRP SPASSPKPGT MGNAIEEEAP ELDLPGPVFV DDFYYDYNFI NFHEDLSYGP
SEEPDLDLAG TGDRTPPPHS HPAAPSTGSP VPATEPPAAK EEGVLGPWSP SPWPSQAGRS
PPPPSEQTPG NPLINFLPEE DTPIGAPDLG LPSLSWPRVS TDGLQTPATP ESQNDFPVGK
DSQSQLPPPW RDRTNEVFKD DEEPKGRGAP HLPPRPSSTL PPLSPVGSTH SSPSPDVAEL
WTGGTVAWEP ALEGGLGPVD SELWPTVGVA SLLPPPIAPL PEMKVRDSSL EPGTPSFPTP
GPGSWDLQTV AVWGTFLPTT LTGLGHMPEP ALNPGPKGQP ESLSPEVPLS SRLLSTPAWD
SPANSHRVPE TQPLAPSLAE AGPPADPLVV RNAGWQAGNW SECSTTCGLG AVWRPVRCSS
GRDEDCAPAG RPQPARRCHL RPCATWHSGN WSKCSRSCGG GSSVRDVQCV DTRDLRPLRP
FHCQPGPAKP PAHRPCGAQP CLSWYTSSWR ECSEACGGGE QQRLVTCPEP GLCEEALRPN
TTRPCNTHPC TQWVVGPWGQ CSGPCGGGVQ RRLVKCVNTQ TGLPEEDSDQ CGHEAWPESS
RPCGTEDCEP VEPPRCERDR LSFGFCETLR LLGRCQLPTI RTQCCRSCSP PSHGAPSRGH
QRVARR
